Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Myeloproliferative Neoplasms

The history of myeloproliferative disorders: before and after Dameshek

Leukemia volume 22, pages 3–13 (2008)Cite this article

Abstract

In 1951, William Dameshek described the concept of ‘myeloproliferative disorders (MPDs)’ by grouping together chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and erythroleukemia; he reasoned that a self-perpetuating trilineage myeloproliferation underlined their pathogenesis. Pre-Dameshek luminaries who laid the foundation for this unifying concept include Bennett, Virchow, Heuck, Vaquez, Osler, Di Guglielmo and Epstein. In 1960, Nowell and Hungerford discovered the Philadelphia (Ph) chromosome in CML. In 1967, Fialkow and colleagues used X-linked polymorphisms to establish CML as a clonal stem cell disease. Also in 1967, the PV Study Group was summoned by Louis Wasserman to study the natural history of PV and conduct large-scale clinical trials. In 1972, Janet Rowley deciphered the Ph chromosome as a reciprocal translocation between chromosomes 9 and 22, thus paving the way for its subsequent characterization as an oncogenic BCR–ABL mutation. In 1996, Brian Druker discovered imatinib—a small molecule ABL inhibitor with exceptional therapeutic activity in CML. In 2005, a gain-of-function JAK2 mutation (JAK2V617F) was described in BCR–ABL-negative MPDs, raising the prospect of a CML-like treatment strategy in PV, ET and PMF. The current review considers these and other landmark events in the history of MPDs.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

References

  1. Bennett JH . Case of hypertrophy of the spleen and liver in which death took place from suppuration of the blood. Edinb Med Surg J 1845; 64: 413–423.

    Google Scholar 

  2. Virchow R . Weisses Blut. Froriep's Notzien 1845; 36: 151–156.

    Google Scholar 

  3. Craigie D . Case of disease and enlargement of the spleen in which death took place from the presence of purulent matter in the blood. Edinb Med Surg J 1845; 64: 400–413.

    Google Scholar 

  4. Vaquez H . Sur une forme speciale de cyanose s'accompanant d'hyperglobulie excessive et peristente (On a special form of cyanosis accompanied by excessive and persistent erythrocytosis). Compt rend Soc de biol and suppl note, Bull et mem Soc med d'hop de Paris, 3 ser 1895; 12: 60 1892; 4: 384–388.

    Google Scholar 

  5. Osler W . Chronic cyanosis, with polycythemia and enlarged spleen: a new clinical entity. Am J Med Sci 1903; 126: 187–201.

    Google Scholar 

  6. Heuck G . Zwei Falle von Leukamie mit eigenthumlichem Blut- resp. Knochenmarksbefund (Two cases of leukemia with peculiar blood and bone marrow findings, respectively). Arch Pathol Anat Physiol Virchows 1879; 78: 475–496.

    Google Scholar 

  7. Epstein E, Goedel A . Hamorrhagische thrombozythamie bei vascularer schrumpfmilz (Hemorrhagic thrombocythemia with a vascular, sclerotic spleen). Virchows Archiv A Pathol Anat Histopathol 1934; 293: 233–248.

    Google Scholar 

  8. Dameshek W . Some speculations on the myeloproliferative syndromes. Blood 1951; 6: 372–375.

    CAS  Google Scholar 

  9. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G . Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 1984; 36: 93–99.

    CAS  Google Scholar 

  10. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005; 7: 387–397.

    Article  CAS  Google Scholar 

  11. James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434: 1144–1148.

    Article  CAS  Google Scholar 

  12. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352: 1779–1790.

    Article  CAS  Google Scholar 

  13. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365: 1054–1061.

    Article  CAS  Google Scholar 

  14. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007; 356: 459–468.

    CAS  Google Scholar 

  15. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3: e270.

    Google Scholar 

  16. Nowell PC, Hungerford DA . Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960; 25: 85–109.

    CAS  Google Scholar 

  17. Rowley JD . Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973; 243: 290–293.

    CAS  Google Scholar 

  18. de Klein A, van Kessel AG, Grosveld G, Bartram CR, Hagemeijer A, Bootsma D et al. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature 1982; 300: 765–767.

    CAS  Google Scholar 

  19. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells. Nat Med 1996; 2: 561–566.

    CAS  Google Scholar 

  20. Cruse JM . History of medicine: the metamorphosis of scientific medicine in the ever-present past. Am J Med Sci 1999; 318: 171–180.

    CAS  Google Scholar 

  21. Falagas ME, Zarkadoulia EA, Bliziotis IA, Samonis G . Science in Greece: from the age of Hippocrates to the age of the genome. FASEB J 2006; 20: 1946–1950.

    CAS  Google Scholar 

  22. Christie RV . Galen on Erasistratus. Perspect Biol Med 1987; 30: 440–449.

    CAS  Google Scholar 

  23. Sigerist HE . A History of Medicine. Oxford University press: New York, 1961; 1: 564.

    Google Scholar 

  24. Fahraeus R . The suspension stability of blood. Acta Med Scand 1921; 55: 1–228.

    Google Scholar 

  25. Avicenna . A treatise on the'Canon of Medicine' of Avicenna (980–1037). Luzac & Co: London, 1930, 276.

    Google Scholar 

  26. Simon SR . Moses Maimonides: medieval physician and scholar. Arch Intern Med 1999; 159: 1841–1845.

    CAS  Google Scholar 

  27. Lieber E . Galen: physician as philosopher; Maimonides: philosopher as physician. Bull Hist Med 1979; 53: 268–285.

    CAS  Google Scholar 

  28. Schmidt PJ . Transfuse George Washington!. Transfusion 2002; 42: 275–277.

    Google Scholar 

  29. Harvey W . Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus. 1628.

  30. Fleming D . Galen on the motions of the blood in the heart and lungs. Isis 1955; 46: 14–21.

    CAS  Google Scholar 

  31. Hooke R . Micrographia: Or, Some Physiological Descriptions of Minute Bodies Made by Magnifying Glasses'. London, J Martyn and J Allestry: London, (1st edn), 1665.

    Google Scholar 

  32. van Leeuwenhoek A . Philosophical transactions of the Royal Society. London 1674; 9: 121–128.

    Google Scholar 

  33. Cobb M . Reading and Writing The Book of Nature: Jan Swammerdam (1637–1680). Endeavour 2000; 24: 122–128.

    Google Scholar 

  34. Lieutaud J . Elementa Physiologiae. Amsterdam (translated and quoted in Dryefus, C 1957, Milestones in the History of Haematology, pp 11–12, New York) 1749, 82–84.

  35. Gulliver G . The works of William Hewson. FRS London, The Sydenham Society 1846; part III, 1vi: 360pp, p 214.

  36. Doyle D . William Hewson (1739–74): the father of haematology. Br J Haematol 2006; 133: 375–381.

    Google Scholar 

  37. Addison W . Colorless globules in the buffy coat of the blood. Lond Med Gaz NS 1840, 1841 27: 477–479.

    Google Scholar 

  38. Donne A . De l'origine des globules du sang, de leur mode de formation et de leur fin. Comptes rendus de l'Académie des Sciences, Paris 1842; 14: 168–366.

    Google Scholar 

  39. Brewer DB . Max Schultze (1865), G. Bizzozero (1882) and the discovery of the platelet. Br J Haematol 2006; 133: 251–258.

    Google Scholar 

  40. Ehrlich P . Beitrag zur Kenntnis der Anilinfarbungen under ihrer Verwendung in der Microscopischen Technik. Archives Mikrochirurgie Anatomischer 1877; 13: 263–277.

    Google Scholar 

  41. Drews J . Paul Ehrlich: magister mundi. Nat Rev Drug Discov 2004; 3: 797–801.

    CAS  Google Scholar 

  42. Piller G . Leukaemia—a brief historical review from ancient times to 1950. Br J Haematol 2001; 112: 282–292.

    CAS  Google Scholar 

  43. Neumann E . Ueber die Bedeutung des Knochenmarkes fur die Blutbildung. Ein Beitrag zur Entwicklungsgeschichte der Blutkorperchen. Archives Heilkunde 1869; 10: 68–102.

    Google Scholar 

  44. Ehrlich P . Uber die Bedeutung der neutrophilen Kornung. Charite Annales 1887; 12: 288–295.

    Google Scholar 

  45. Askanazy M . Ueber extrauterine Bildung von Blutzellen in der Leber. Verh Dtsch Pathol Ges 1904; 7: 58–65.

    Google Scholar 

  46. Assmann H . Beitrage zur osteosklerotischen anamie. Beitr Pathol Anat Allgemeinen Pathologie (Jena) 1907; 41: 565–595.

    Google Scholar 

  47. Meyer E, Heinke A . Uber Blutbildung bei schweren Anamien und Leukamien. Dtsch Arch Klin Med 1907; 88: 435–492.

    Google Scholar 

  48. Donhauser J . The human spleen as an haematoplastic organ, as exemplified in a case of splenomegaly with sclerosis of the bone-marrow. J Exp Med 1908; 10: 559–574.

    CAS  Google Scholar 

  49. Hirschfeld H . Die generalisierte aleukamische Myelose und ihre Stellung im System der leukamischen Erkrankungen. Z Klin Med 1914; 80: 126–173.

    Google Scholar 

  50. Jackson H Jr, Parker F Jr, Lemon HM . Agnogenic myeloid metaplasia of the spleen: a syndrome simulating other more definite hematological disorders. N Engl J Med 1940; 222: 985–994.

    Google Scholar 

  51. Jaffe ES, Harris NL, Stein H, Vardiman JW . World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissues. IARC Press: Lyon, France, 2001, 1–351.

    Google Scholar 

  52. Mesa RA, Verstovsek S, Cervantes F, Barosi G, Reilly JT, Dupriez B et al. Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF-BP): Consensus on terminology by the international working group for myelofibrosis research and treatment (IWG-MRT). Leuk Res 2007; 31: 737–740.

    Google Scholar 

  53. Hirsch R . Generalized osteosclerosis with chronic polycythemia vera. Arch Pathol 1935; 19: 91–97.

    Google Scholar 

  54. Vaughan JM, Harrison CV . Leuco-erythrobalstic anaemia and myelosclerosis. J Pathol Bacteriol 1939; 48: 339–352.

    Google Scholar 

  55. Rosenthal N, Erf LA . Clinical observations on osteopetrosis and myelofibrosis. Arch Intern Med 1943; 71: 793–813.

    Google Scholar 

  56. Heller EL, Lewisohn MG, Palin WE . Aleukemic myelosis: chronic nonleukemic myelosis, agnogenic myeloid metaplasia, osteosclerosis, leuko-erythroblastic anemia, and synonymous designations. Am J Pathol 1947; 23: 327–365.

    CAS  Google Scholar 

  57. Silverstein MN . Agnogenic myeloid metaplasia. 1975, 126.

  58. Cabot RC . A case of chronic cyanosis without discernible cause, ending in cerebral hemorrhage. Boston Med Surg J 1899; 141: 574–575.

    Google Scholar 

  59. Cabot RC . A second case of chronic cyanosis without assignable cause. Boston Med Sug J 1900; 142: 275.

    Google Scholar 

  60. McKeen SF . A case of marked cyanosis, difficult to explain. Boston Med Surg J 1901; 144: 610.

    Google Scholar 

  61. Saundby R, Russell AE . An unexplained condition of chronic cyanosis, with a report of a case. Lancet 1902; 1: 515.

    Google Scholar 

  62. Robb-Smith AHT . Osler's influence on haematology. Blood Cells 1981; 7: 513–533.

    CAS  Google Scholar 

  63. Osler W . A clinical lecture on erythraemia (polycythaemia with cyanosis, maladie de Vaquez). Lancet 1908; 1: 143–146.

    Google Scholar 

  64. Turk W . Beitrage zur kenntnis des symptomenbildes polyzythamie mit milztumor und zyanose. Wiener medizinische Wochenschrift 1904; 17: 153–160, 189–193.

    Google Scholar 

  65. Weber FP, Watson JH . Chronic polycythemia with enlarged spleen, probably a disease of the bone marrow. Trans Clin Soc 1904; 37: 115.

    Google Scholar 

  66. Parkes-Weber F . Polycythemia, erythrocytosis and erythraemia. QJM 1908; 2: 85–134.

    Google Scholar 

  67. Di Guglielmo G . Richerche di ematologia. I. Un caso di eritroleucemia. Megacariociti in circolo e loro funzione piastrinopoietico. Folia Med (Pavia) 1917; 13: 386.

    Google Scholar 

  68. Di Guglielmo G . Eritremie acute. Bolletino della Societa di Medicina e Chirugia di pavia 1923; 40: 665.

    Google Scholar 

  69. Di Guglielmo G . Myelosi eritremica cronica. Haematologica 1942; 24: 1–58.

    Google Scholar 

  70. Martin WJ, Bayrd ED . Erythroleukemia, with special emphasis on the acute or incomplete variety; report of five cases. Blood 1954; 9: 321–339.

    CAS  Google Scholar 

  71. Vardiman JW, Harris NL, Brunning RD . The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002; 100: 2292–2302.

    CAS  Google Scholar 

  72. Di Guglielmo G . Eritroleucemia e pistrinemia. Folia Med 1920; 1: 36.

    Google Scholar 

  73. Fanger H, Cella Jr LJ, Litchman H . Thrombocythemia; report of three cases and review of literature. N Engl J Med 1954; 250: 456–461.

    CAS  Google Scholar 

  74. Gunz FW . Hemorrhagic thrombocythemia: a critical review. Blood 1960; 15: 706–723.

    CAS  Google Scholar 

  75. Ozer FL, Traux WE, Miesch DC, Levin WC . Primary hemorrhagic thrombocythemia. Am J Med 1960; 28: 807–823.

    CAS  Google Scholar 

  76. Gunz FW . William Dameshek, 1900–1969. Blood 1970; 35: 577–582.

    CAS  Google Scholar 

  77. Stratton HM . William Dameshek, a personal remembrance. Blood 1970; 35: 4–5.

    CAS  Google Scholar 

  78. Jaffe ER . Commentary: the evolution of the American and International Societies of Hematology: a brief history. Am J Hematol 1992; 39: 67–69.

    CAS  Google Scholar 

  79. Tullis JL . William Dameshek, 1900–1969. Blood 1970; 35: 1–3.

    CAS  Google Scholar 

  80. Parkes-Weber F, Watson JH . Chronic polycythemia with enlarged spleen, probably a disease of the bone marrow. Br J Med 1904; 1: 729.

    Google Scholar 

  81. Pianese G . Per una miglior conoscenza dei megacariociti. Haematologica 1920; 1: 61–110.

    Google Scholar 

  82. Minot GR, Buckman TE . Erythremia (polycythemia rubra vera). The development of anemia; the relation to leukemia; consideration of the basal metabolism, blood formation and destruction and fragility of the red cells. Am J Med Sci 1923; 166: 469–489.

    Google Scholar 

  83. Nowell PC . Progress with chronic myelogenous leukemia: a personal perspective over four decades. Annu Rev Med 2002; 53: 1–13.

    CAS  Google Scholar 

  84. Hsu TC, Pomerat CM . Mammalian chromosomes in vitro II. A method for spreading the chromosomes of cells in tissue culture. J Hered 1953; 44: 23–29.

    Google Scholar 

  85. Nowell PC, Hungerford DA . A minute chromosome in human granulocytic leukemia. Science 1960; 132: 1497.

    Google Scholar 

  86. Tjio J-H, Levan A . The chromosome number of man. Hereditas 1956; 42: 1–6.

    Google Scholar 

  87. Lejeune J, Gautier M, Turpin R . Etude des chromosomes somatiques de neuf enfants mongoliens. CR Seances Acad Sci 1959; 248: 1721–1722.

    CAS  Google Scholar 

  88. Boveri T . Zur Frage der Entstehung maligner Tumoren. Gustav Fischer, Jena 1914.

  89. Beutler E, Yeh M, Fairbanks VF . The normal human female as a mosaic of X-chromosome activity: studies using the gene for C-6-PD-deficiency as a marker. Proc Natl Acad Sci USA 1962; 48: 9–16.

    CAS  Google Scholar 

  90. Lyon MF . Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 1961; 190: 372–373.

    CAS  Google Scholar 

  91. Ohno S, Makino S . The single-X nature of sex chromatin in man. Lancet 1961; 1: 78–79.

    CAS  Google Scholar 

  92. Ohno S, Hauschka TS . Allocycly of the X-chromosome in tumors and normal tissues. Cancer Res 1960; 20: 541–545.

    CAS  Google Scholar 

  93. Linder D, Gartler SM . Glucose-6-phosphate dehydrogenase mosaicism: utilization as a cell marker in the study of leiomyomas. Science 1965; 150: 67–69.

    CAS  Google Scholar 

  94. Fialkow PJ, Gartler SM, Yoshida A . Clonal origin of chronic myelocytic leukemia in man. Proc Natl Acad Sci USA 1967; 58: 1468–1471.

    CAS  Google Scholar 

  95. Adamson JW, Fialkow PJ, Murphy S, Prchal JF, Steinmann L . Polycythemia vera: stem-cell and probable clonal origin of the disease. N Engl J Med 1976; 295: 913–916.

    CAS  Google Scholar 

  96. Jacobson RJ, Salo A, Fialkow PJ . Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis. Blood 1978; 51: 189–194.

    CAS  Google Scholar 

  97. Fialkow PJ, Faguet GB, Jacobson RJ, Vaidya K, Murphy S . Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell. Blood 1981; 58: 916–919.

    CAS  Google Scholar 

  98. Martin PJ, Najfeld V, Hansen JA, Penfold GK, Jacobson RJ, Fialkow PJ . Involvement of the B-lymphoid system in chronic myelogenous leukaemia. Nature 1980; 287: 49–50.

    CAS  Google Scholar 

  99. Raskind WH, Jacobson R, Murphy S, Adamson JW, Fialkow PJ . Evidence for the involvement of B lymphoid cells in polycythemia vera and essential thrombocythemia. J Clin Invest 1985; 75: 1388–1390.

    CAS  Google Scholar 

  100. Reeder TL, Bailey RJ, Dewald GW, Tefferi A . Both B and T lymphocytes may be clonally involved in myelofibrosis with myeloid metaplasia. Blood 2003; 101: 1981–1983.

    CAS  Google Scholar 

  101. Tefferi A, Schad CR, Pruthi RK, Ahmann GJ, Spurbeck JL, Dewald GW . Fluorescent in situ hybridization studies of lymphocytes and neutrophils in chronic granulocytic leukemia. Cancer Genet Cytogenet 1995; 83: 61–64.

    CAS  Google Scholar 

  102. Buschle M, Janssen JW, Drexler H, Lyons J, Anger B, Bartram CR . Evidence for pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation. Leukemia 1988; 2: 658–660.

    CAS  Google Scholar 

  103. Pardanani A, Lasho TL, Finke C, Markovic SN, Tefferi A . Demonstration of MPLW515K, but not JAK2V617F, in in vitro expanded CD4+ T lymphocytes. Leukemia advance online publication 17 May 2007; doi: 101038/sjleu2404749 2007.

  104. Bellanne-Chantelot C, Chaumarel I, Labopin M, Bellanger F, Barbu V, De Toma C et al. Genetic and clinical implications of the Val617Phe JAK2 mutation in 72 families with myeloproliferative disorders. Blood 2006; 108: 346–352.

    CAS  Google Scholar 

  105. Raskind WH, Ferraris AM, Najfeld V, Jacobson RJ, Moohr JW, Fialkow PJ . Further evidence for the existence of a clonal Ph-negative stage in some cases of Ph-positive chronic myelocytic leukemia. Leukemia 1993; 7: 1163–1167.

    CAS  Google Scholar 

  106. Kovitz C, Kantarjian H, Garcia-Manero G, Abruzzo LV, Cortes J . Myelodysplastic syndromes and acute leukemia developing after imatinib mesylate therapy for chronic myeloid leukemia. Blood 2006; 108: 2811–2813.

    CAS  Google Scholar 

  107. Kralovics R, Teo SS, Li S, Theocharides A, Buser AS, Tichelli A et al. Acquisition of the V617F mutation of JAK2 is a late genetic event in a subset of patients with myeloproliferative disorders. Blood 2006; 108: 1377–1380.

    CAS  Google Scholar 

  108. Pardanani A, Lasho TL, Finke C, Mesa RA, Hogan WJ, Ketterling RP et al. Extending JAK2V617F and MPLW515 mutation analysis to single hematopoietic colonies and B- and T-lymphocytes. Stem Cells 2007; Published online June 1, 2007, DOI:10.1634/stemcells.2007-0175.

    CAS  Google Scholar 

  109. Harrison CN, Gale RE, Machin SJ, Linch DC . A large proportion of patients with a diagnosis of essential thrombocythemia do not have a clonal disorder and may be at lower risk of thrombotic complications. Blood 1999; 93: 417–424.

    CAS  Google Scholar 

  110. Antonioli E, Guglielmelli P, Pancrazzi A, Bogani C, Verrucci M, Ponziani V et al. Clinical implications of the JAK2 V617F mutation in essential thrombocythemia. Leukemia 2005; 19: 1847–1849.

    CAS  Google Scholar 

  111. Wasserman LR . Polycythemia Vera Study Group: a historical perspective. Semin Hematol 1986; 23: 183–187.

    CAS  Google Scholar 

  112. Tinney WS, Hall BE, Giffen HZ . Hematologic complications of P. Vera. Proc Staff Meet Mayo Clin 1943; 18: 227–230.

    Google Scholar 

  113. Hall BE . Therapeutic use of radiophosphorus in polycythemia vera, leukemia and allied diseases. In: The Use of Isotopes in Biology and Medicine. University of Wisconsin Press: WI, 1948, 353–376.

    Google Scholar 

  114. Ludin M . Ein betrag zur kentniss der symptmologie und therapie der primaren polycythemie. Z Klin Med 1917; 84: 460–476.

    Google Scholar 

  115. Eppinger H, Kloss K . Zur Therapie der Polyzythaemie. Therapeutis du Monatshefte 1918; 32: 322–326.

    Google Scholar 

  116. Forkner CE, Scott TFM, Wu SC . Treatment of polycythemia vera (erythremia) with a solution of potassium arsenite. Arch Intern Med 1933; 51: 616–629.

    CAS  Google Scholar 

  117. Lawrence JH . Nuclear physics and therapy: preliminary report on a new method for the treatment of leukemia and polycythemia vera. Radiology 1940; 35: 51–60.

    CAS  Google Scholar 

  118. Falconer EH . The treatment of polycythemia vera with lead compounds. Am J Med 1942; 203: 856–857.

    Google Scholar 

  119. Shullenberger CC, Watkins CH . Effects of nitrogen mustard on the bone marrow in polycythemia vera. Ann Intern Med 1950; 33: 841–853.

    CAS  Google Scholar 

  120. Rosenthal N, Rosenthal RL . Treatment of polycythemia vera with triethylene melamine: summary of thirty cases. Arch Intern Med 1952; 90: 379.

    CAS  Google Scholar 

  121. Isaacs R . Treatment of polycythemia vera with daraprim. J Am Med Assoc 1954; 156: 1491–1493.

    CAS  Google Scholar 

  122. Wald N, Hoshino T, Sears ME . Therapy of polycythemia vera with myleran. Blood 1958; 13: 757–762.

    CAS  Google Scholar 

  123. Shullenberger CC . Long-range treatment of polycythemia vera with 6-mercaptopurine. Cancer Chemother Rep 1962; 16: 251–252.

    CAS  Google Scholar 

  124. Bond WH . Evaluation of compound 8103 Abbott (N, N′ bis (bromopropionyl) piperazine) in the treatment of polycythemia rubra vera. Proc Am Assoc Cancer Res 1962; 3: 306.

    Google Scholar 

  125. Perkins J, Israuels MC, Wilkinson JF . Polycythaemia vera: clinical studies on a series of 127 patients managed without radiation therapy. QJM 1964; 33: 499–518.

    CAS  Google Scholar 

  126. Varela JE, Kremenchuzky S, Fraga A, Etcheverry MA, Figueiras H . Evaluation of haemopoiesis and comparative study of 32P and chlorambucil therapy by means of radiotracers in polycythemia vera. Minerva Nucl 1965; 9: 275–280.

    CAS  Google Scholar 

  127. Pengelly CD . Reduction of haematocrit and red-blood-cell volume in patients with polycythaemia secondary to hypoxic lung disease by dapsone and pyrimethamine. Lancet 1966; 2: 1381–1386.

    CAS  Google Scholar 

  128. West WO, Ruff JD, Yarboro JW . Response of polycythemia to treatment with a new agent: hydroxyurea (abstract). Ann Intern Med 1970; 72: 795.

    Google Scholar 

  129. Logue GL, Gutterman JU, McGinn TG, Laszlo J, Rundles RW . Melphalan therapy of polycythemia vera. Blood 1970; 36: 70–86.

    CAS  Google Scholar 

  130. Osler W . Chronic cyanosis with polycythemia and enlarged spleen: a new clinical entity. Am J Sci 1903; 126: 187–201.

    Google Scholar 

  131. Chievitz E, Thiede T . Complications and causes of death in polycythemia vera. Acta Med Scand 1962; 172: 513–523.

    CAS  Google Scholar 

  132. Berk PD, Wasserman LR, Fruchtman SM, Goldberg JD . Treatment of polycythemia vera: a summary of clinical trials conducted by the Polycythemia Vera Study Group. In: Wasserman LR, Berk PD, Berlin NI (eds). Polycythemia Vera and the Myeloproliferative Disorders. W.B. Saunders: Philadelphia, 1995, 166–194.

    Google Scholar 

  133. Fruchtman SM, Mack K, Kaplan ME, Peterson P, Berk PD, Wasserman LR . From efficacy to safety—a Polycythemia Vera Study Group report on hydroxyurea in patients with polycythemia vera. Semin Hematol 1997; 34: 17–23.

    CAS  Google Scholar 

  134. Tartaglia AP, Goldberg JD, Berk PD, Wasserman LR . Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera. Semin Hematol 1986; 23: 172–176.

    CAS  Google Scholar 

  135. Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004; 350: 114–124.

    CAS  Google Scholar 

  136. Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. 10.1182/blood-2007-04-083501. Blood 2007: 110: 1092–1097.

    CAS  Google Scholar 

  137. Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Eng J Med 1995; 332: 1132–1136.

    CAS  Google Scholar 

  138. Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 2005; 353: 33–45.

    CAS  Google Scholar 

  139. Gangat N, Wolanskyj AP, McClure RF, Li CY, Schwager S, Wu W et al. Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia 2007; 21: 270–276.

    CAS  Google Scholar 

  140. Finazzi G, Caruso V, Marchioli R, Capnist G, Chisesi T, Finelli C et al. Acute leukemia in polycythemia vera. An analysis of 1,638 patients enrolled in a prospective observational study. Blood 2005; 105: 2664–2670.

    CAS  Google Scholar 

  141. Berlin NI . Prologue—polycythemia vera—the closing of the Wasserman–Polycythemia Vera Study Group era. Semin Hematol 1997; 34: 1–5.

    CAS  Google Scholar 

  142. Seabright M . A rapid banding technique for human chromosomes. Lancet 1971; 2: 971–972.

    CAS  Google Scholar 

  143. Caspersson T, Zech L, Johansson C . Differential binding of alkylating fluorochromes in human chromosomes. Exp Cell Res 1970; 60: 315–319.

    CAS  Google Scholar 

  144. Caspersson T, Gahrton G, Lindsten J, Zech L . Identification of the Philadelphia chromosome as a number 22 by quinacrine mustard fluorescence analysis. Exp Cell Res 1970; 63: 238–240.

    CAS  Google Scholar 

  145. Rowley JD, Golomb HM, Dougherty C . 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet 1977; 1: 549–550.

    CAS  Google Scholar 

  146. Rowley JD . Identificaton of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet 1973; 16: 109–112.

    CAS  Google Scholar 

  147. Abelson HT, Rabstein LS . Lymphosarcoma: virus-induced thymic-independent disease in mice. Cancer Res 1970; 30: 2213–2222.

    CAS  Google Scholar 

  148. Heisterkamp N, Groffen J, Stephenson JR, Spurr NK, Goodfellow PN, Solomon E et al. Chromosomal localization of human cellular homologues of two viral oncogenes. Nature 1982; 299: 747–749.

    CAS  Google Scholar 

  149. Heisterkamp N, Stam K, Groffen J, de Klein A, Grosveld G . Structural organization of the bcr gene and its role in the Ph' translocation. Nature 1985; 315: 758–761.

    CAS  Google Scholar 

  150. Canaani E, Gale RP, Steiner-Saltz D, Berrebi A, Aghai E, Januszewicz E . Altered transcription of an oncogene in chronic myeloid leukaemia. Lancet 1984; 1: 593–595.

    CAS  Google Scholar 

  151. Collins SJ, Kubonishi I, Miyoshi I, Groudine MT . Altered transcription of the c-abl oncogene in K-562 and other chronic myelogenous leukemia cells. Science 1984; 225: 72–74.

    CAS  Google Scholar 

  152. Shtivelman E, Lifshitz B, Gale RP, Canaani E . Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 1985; 315: 550–554.

    CAS  Google Scholar 

  153. Stam K, Heisterkamp N, Grosveld G, de Klein A, Verma RS, Coleman M et al. Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome. N Engl J Med 1985; 313: 1429–1433.

    CAS  Google Scholar 

  154. Ben-Neriah Y, Daley GQ, Mes-Masson AM, Witte ON, Baltimore D . The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. Science 1986; 233: 212–214.

    CAS  Google Scholar 

  155. Erikson J, Griffin CA, ar-Rushdi A, Valtieri M, Hoxie J, Finan J et al. Heterogeneity of chromosome 22 breakpoint in Philadelphia-positive (Ph+) acute lymphocytic leukemia. Proc Natl Acad Sci USA 1986; 83: 1807–1811.

    CAS  Google Scholar 

  156. Chan LC, Karhi KK, Rayter SI, Heisterkamp N, Eridani S, Powles R et al. A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia. Nature 1987; 325: 635–637.

    CAS  Google Scholar 

  157. Hermans A, Heisterkamp N, von Linden M, van Baal S, Meijer D, van der Plas D et al. Unique fusion of bcr and c-abl genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell 1987; 51: 33–40.

    CAS  Google Scholar 

  158. Clark SS, McLaughlin J, Crist WM, Champlin R, Witte ON . Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL. Science 1987; 235: 85–88.

    CAS  Google Scholar 

  159. McLaughlin J, Chianese E, Witte ON . In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome. Proc Natl Acad Sci USA 1987; 84: 6558–6562.

    CAS  Google Scholar 

  160. Daley GQ, Baltimore D . Transformation of an interleukin 3-dependent hematopoietic cell line by the chronic myelogenous leukemia-specific P210bcr/abl protein. Proc Natl Acad Sci USA 1988; 85: 9312–9316.

    CAS  Google Scholar 

  161. Konopka JB, Watanabe SM, Witte ON . An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell 1984; 37: 1035–1042.

    CAS  Google Scholar 

  162. Hariharan IK, Harris AW, Crawford M, Abud H, Webb E, Cory S et al. A bcr-v-abl oncogene induces lymphomas in transgenic mice. Mol Cell Biol 1989; 9: 2798–2805.

    CAS  Google Scholar 

  163. Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J . Acute leukaemia in bcr/abl transgenic mice. Nature 1990; 344: 251–253.

    CAS  Google Scholar 

  164. Kelliher MA, McLaughlin J, Witte ON, Rosenberg N . Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci USA 1990; 87: 6649–6653.

    CAS  Google Scholar 

  165. Daley GQ, Van Etten RA, Baltimore D . Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 1990; 247: 824–830.

    CAS  Google Scholar 

  166. Elefanty AG, Hariharan IK, Cory S . bcr–abl, the hallmark of chronic myeloid leukaemia in man, induces multiple haemopoietic neoplasms in mice. EMBO J 1990; 9: 1069–1078.

    CAS  Google Scholar 

  167. Galton DA . Myleran in chronic myeloid leukaemia; results of treatment. Lancet 1953; 264: 208–213.

    CAS  Google Scholar 

  168. Kennedy BJ, Yarbro JW . Metabolic and therapeutic effects of hydroxyurea in chronic myelogenous leukemia. Trans Assoc Am Physicians 1965; 78: 391–399.

    CAS  Google Scholar 

  169. Talpaz M, McCredie KB, Mavligit GM, Gutterman JU . Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia. Blood 1983; 62: 689–692.

    CAS  Google Scholar 

  170. Valentiner W . Ein Symptomatisch ausgezichneter Fall von Leucaemie. Berl Klin Wochenschr 1865; 2: 320–321.

    Google Scholar 

  171. Lissauer H . Zwei Falle von Leucaemie. Berl Klin Wochenschr 1865; 2: 403–404.

    Google Scholar 

  172. Senn N . Case of splenomedullary leukaemia successfully treated by the use of the Rontgen ray. Med Rec 1903; 64: 281–282.

    Google Scholar 

  173. Forkner CE, Scott TFM . Arsenic as a therapeutic agent in chronic myelogenous leukemia. JAMA 1931; 97: 3–5.

    Google Scholar 

  174. Hueper WC, Russell M . Some immunological aspects of leukemia. Arch Intern Med 1932; 49: 113–122.

    Google Scholar 

  175. Kalapos I . Die Wirkung des Benzols bei der Leukamie. Klin Wochenschr 1935; 14: 864–867.

    CAS  Google Scholar 

  176. Cooper T, Watkins CH . Ethyl carbamate (urethane) in the treatment of chronic myelocytic leukemia; results of a three-year study. Med Clin North Am 1950; 34: 1205–1215.

    CAS  Google Scholar 

  177. Osgood EE, Seaman AJ . Treatment of chronic leukemias. Results of therapy by titrated, regularly spaced total body radioactive phosphorus, or roentgen irradiation. JAMA 1952; 150: 1372–1379.

    CAS  Google Scholar 

  178. Shay H, Gruenstein M, Harris C . The effect of triethylene thiophosphoramide (thio-TEPA) in the treatment of chronic myelocytic chloroleukemia in the rat. J Natl Cancer Inst 1954; 15: 463–481.

    CAS  Google Scholar 

  179. Buckner D, Graw Jr RG, Eisel RJ, Henderson ES, Perry S . Leukapheresis by continuous flow centrifugation (CFC) in patients with chronic myelocytic leukemia (CML). Blood 1969; 33: 353–369.

    CAS  Google Scholar 

  180. Cutting HO . The effect of splenectomy in chronic granulocytic leukemia. Report of a case. Arch Intern Med 1967; 120: 356–360.

    CAS  Google Scholar 

  181. Tura S, Baccarani M, Mandelli F, Amadori S, Cajozzo A, di Marco P et al. Splenectomy in early chronic myeloid leukaemia: preliminary report on 37 cases. Haematologica 1974; 59: 428–439.

    CAS  Google Scholar 

  182. Baker MA, Taub RN, Carter Jr WH, Davidson M, Sutton DM, Kutas G et al. Immunotherapy for chronic myelogenous leukemia: survival not affected by treatment in the stable phase. Cancer Res 1984; 44: 383–385.

    CAS  Google Scholar 

  183. Cunningham I, Gee T, Dowling M, Chaganti R, Bailey R, Hopfan S et al. Results of treatment of Ph′+ chronic myelogenous leukemia with an intensive treatment regimen (L-5 protocol). Blood 1979; 53: 375–395.

    CAS  Google Scholar 

  184. Kantarjian HM, Vellekoop L, McCredie KB, Keating MJ, Hester J, Smith T et al. Intensive combination chemotherapy (ROAP 10) and splenectomy in the management of chronic myelogenous leukemia. J Clin Oncol 1985; 3: 192–200.

    CAS  Google Scholar 

  185. Chronic granulocytic leukaemia: comparison of radiotherapy and busulphan therapy. Report of the Medical Research Council's working party for therapeutic trials in leukaemia. BMJ 1968; 1: 201–208.

    Google Scholar 

  186. Frommeyer Jr WB . Comparison of cyclophosphamide (cytoxan and uracil mustard (U-8344) in chronic granulocytic leukemia. Cancer 1964; 17: 288–296.

    Google Scholar 

  187. Kaung DT, Close HP, Whittington RM, Patno ME . Comparison of busulfan and cyclophosphamide in the treatment of chronic myelocytic leukemia. Cancer 1971; 27: 608–612.

    CAS  Google Scholar 

  188. Minot GR, Buckman TE, Isaacs R . Chronic myelogenous leukemia. Age, incidence, duration, and benefit derived from radiation. JAMA 1924; 82: 1489–1494.

    Google Scholar 

  189. Goeddel DV, Yelverton E, Ullrich A, Heyneker HL, Miozzari G, Holmes W et al. Human leukocyte interferon produced by E. coli is biologically active. Nature 1980; 287: 411–416.

    CAS  Google Scholar 

  190. Talpaz M, Kantarjian HM, McCredie K, Trujillo JM, Keating MJ, Gutterman JU . Hematologic remission and cytogenetic improvement induced by recombinant human interferon alpha A in chronic myelogenous leukemia. N Engl J Med 1986; 314: 1065–1069.

    CAS  Google Scholar 

  191. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. The Italian Cooperative Study Group on chronic myeloid leukemia. N Engl J Med 1994; 330: 820–825.

    Google Scholar 

  192. Hehlmann R, Heimpel H, Hasford J, Kolb HJ, Pralle H, Hossfeld DK et al. Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group. Blood 1993; 82: 398–407.

    CAS  Google Scholar 

  193. Robin M, Guardiola P, Devergie A, Yeshurun M, Shapiro S, Esperou H et al. A 10-year median follow-up study after allogeneic stem cell transplantation for chronic myeloid leukemia in chronic phase from HLA-identical sibling donors. Leukemia 2005; 19: 1613–1620.

    CAS  Google Scholar 

  194. Buchdunger E, Zimmermann J, Mett H, Meyer T, Muller M, Druker BJ et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res 1996; 56: 100–104.

    CAS  Google Scholar 

  195. Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J . Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 2000; 289: 1938–1942.

    CAS  Google Scholar 

  196. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348: 994–1004.

    CAS  Google Scholar 

  197. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355: 2408–2417.

    CAS  Google Scholar 

  198. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM et al. Activity of a specific inhibitor of the BCR–ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344: 1038–1042.

    CAS  Google Scholar 

  199. Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL . Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004; 305: 399–401.

    CAS  Google Scholar 

  200. Azam M, Nardi V, Shakespeare WC, Metcalf III CA, Bohacek RS, Wang Y et al. Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Proc Natl Acad Sci USA 2006; 103: 9244–9249.

    CAS  Google Scholar 

  201. Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006; 354: 2542–2551.

    Google Scholar 

  202. Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006; 354: 2531–2541.

    CAS  Google Scholar 

  203. Druker BJ . Circumventing resistance to kinase-inhibitor therapy. N Engl J Med 2006; 354: 2594–2596.

    CAS  Google Scholar 

  204. Carter TA, Wodicka LM, Shah NP, Velasco AM, Fabian MA, Treiber DK et al. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci USA 2005; 102: 11011–11016.

    CAS  Google Scholar 

  205. Verstovsek S, Silver RT, Cross NC, Tefferi A . JAK2V617F mutational frequency in polycythemia vera: 100%, >90%, less? Leukemia 2006; 20: 2067.

    CAS  Google Scholar 

  206. Tefferi A, Lasho TL, Schwager SM, Strand JS, Elliott M, Mesa R et al. The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera. Cancer 2006; 106: 631–635.

    CAS  Google Scholar 

  207. James C, Delhommeau F, Marzac C, Teyssandier I, Couedic JP, Giraudier S et al. Detection of JAK2 V617F as a first intention diagnostic test for erythrocytosis. Leukemia 2006; 20: 350–353.

    CAS  Google Scholar 

  208. Tefferi A, Strand JJ, Lasho TL, Knudson RA, Finke CM, Gangat N et al. Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera. Leukemia 2007; 21: 2074–2075.

    CAS  Google Scholar 

  209. Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT et al. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet 2005; 366: 1945–1953.

    CAS  Google Scholar 

  210. Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol 2005; 131: 208–213.

    CAS  Google Scholar 

  211. Kittur J, Knudson RA, Lasho TL, Finke CM, Gangat N, Wolanskyj AP et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer 2007; 109: 2279–2284.

    Google Scholar 

  212. Tefferi A, Lasho TL, Schwager SM, Steensma DP, Mesa RA, Li CY et al. The JAK2 tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Br J Haematol 2005; 131: 320–328.

    CAS  Google Scholar 

  213. Renneville A, Quesnel B, Charpentier A, Terriou L, Crinquette A, Lai JL et al. High occurrence of JAK2 V617 mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Leukemia 2006; 20: 2067–2070.

    CAS  Google Scholar 

  214. Wang SA, Hasserjian RP, Loew JM, Sechman EV, Jones D, Hao S et al. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features. Leukemia 2006; 20: 1641–1644.

    Google Scholar 

  215. Vizmanos JL, Ormazabal C, Larrayoz MJ, Cross NC, Calasanz MJ . JAK2 V617F mutation in classic chronic myeloproliferative diseases: a report on a series of 349 patients. Leukemia 2006; 20: 534–535.

    CAS  Google Scholar 

  216. Kremer M, Horn T, Dechow T, Tzankov A, Quintanilla-Martinez L, Fend F . The JAK2 V617F mutation occurs frequently in myelodysplastic/myeloproliferative diseases, but is absent in true myelodysplastic syndromes with fibrosis. Leukemia 2006; 20: 1315–1316.

    CAS  Google Scholar 

  217. Steensma DP, McClure RF, Karp JE, Tefferi A, Lasho TL, Powell HL et al. JAK2 V617F is a rare finding in de novo acute myeloid leukemia, but STAT3 activation is common and remains unexplained. Leukemia 2006; 20: 971–978.

    CAS  Google Scholar 

  218. Nishii K, Nanbu R, Lorenzo VF, Monma F, Kato K, Ryuu H et al. Expression of the JAK2 V617F mutation is not found in de novo AML and MDS but is detected in MDS-derived leukemia of megakaryoblastic nature. Leukemia 2007; 21: 1337–1338.

    CAS  Google Scholar 

  219. Steensma DP, Dewald GW, Lasho TL, Powell HL, McClure RF, Levine RL et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both ‘atypical’ myeloproliferative disorders and myelodysplastic syndromes. Blood 2005; 106: 1207–1209.

    CAS  Google Scholar 

  220. Fiorini A, Farina G, Reddiconto G, Palladino M, Rossi E, Za T et al. Screening of JAK2 V617F mutation in multiple myeloma. Leukemia 2006; 20: 1912–1913.

    CAS  Google Scholar 

  221. Melzner I, Weniger MA, Menz CK, Moller P . Absence of the JAK2 V617F activating mutation in classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Leukemia 2006; 20: 157–158.

    CAS  Google Scholar 

  222. Tefferi A, Vardiman JW . The diagnostic interface between histology and molecular tests in myeloproliferative disorders. Curr Opin Hematol 2007; 14: 115–122.

    Google Scholar 

  223. Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108: 3472–3476.

    CAS  Google Scholar 

  224. Lasho TL, Pardanani A, McClure RF, Mesa RA, Levine RL, Gary Gilliland D et al. Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over time. Br J Haematol 2006; 135: 683–687.

    CAS  Google Scholar 

  225. Pardanani A, Lasho TL, Finke C, Hanson CA, Tefferi A . Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia 2007; 21: 1960–1963.

    CAS  Google Scholar 

  226. Tefferi A, Gilliland DG . Oncogenes in myeloproliferative disorders. Cell Cycle 2007; 6: 550–566.

    CAS  Google Scholar 

  227. Tefferi A, Pardanani A . Evaluation of ‘increased’ hemoglobin in the JAK2 mutations era: a diagnostic algorithm based on genetic tests. Mayo Clin Proc 2007; 82: 599–604.

    CAS  Google Scholar 

  228. Tefferi A . JAK2 mutations in polycythemia vera—molecular mechanisms and clinical applications. N Engl J Med 2007; 356: 444–445.

    CAS  Google Scholar 

  229. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003; 348: 1201–1214.

    CAS  Google Scholar 

  230. Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter EJ et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002; 347: 481–487.

    CAS  Google Scholar 

  231. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347: 472–480.

    CAS  Google Scholar 

  232. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783–792.

    CAS  Google Scholar 

  233. Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369: 29–36.

    CAS  Google Scholar 

  234. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 235–242.

    CAS  Google Scholar 

  235. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988; 72: 567–572.

    CAS  Google Scholar 

  236. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997; 337: 1021–1028.

    CAS  Google Scholar 

  237. Pardanani A, Hood J, Lasho T, Levine RL, Martin MB, Noronha G et al. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L//K mutations. Leukemia 2007: 21: 1658–1668.

    CAS  Google Scholar 

  238. Niblack J . http://www.mpdinfo.org/:, accessed June 15, 2007.

  239. Rosen R . http://www.mpdfoundation.org/:, accessed June 15, 2007.

  240. Landro L . The Growing Clout Of Online Patient Groups. The Wall Street Journal 2007; 6/13/2007: http://online.wsj.com/article/SB118168968368633094.html.

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    A Tefferi

Authors
  1. A Tefferi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Tefferi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Tefferi, A. The history of myeloproliferative disorders: before and after Dameshek. Leukemia 22, 3–13 (2008). https://doi.org/10.1038/sj.leu.2404946

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404946

Keywords

  • historical
  • myeloid
  • MPD
  • JAK2-V617F
  • V617F

This article is cited by

Search

Advanced search

Quick links