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Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia – a cDNA array study

Leukemia volume 16, pages 2213–2221 (2002)Cite this article

Abstract

Several specific cytogenetic changes are known to be associated with childhood acute lymphoblastic leukemia (ALL), and many of them are important prognostic factors for the disease. Little is known, however, about the changes in gene expression in ALL. Recently, the development of cDNA array technology has enabled the study of expression of hundreds to thousands of genes in a single experiment. We used the cDNA array method to study the gene expression profiles of 17 children with precursor-B ALL. Normal B cells from adenoids were used as reference material. We discuss the 25 genes that were most over-expressed compared to the reference. These included four genes that are normally expressed only in the myeloid lineages of the hematopoietic cells: RNASE2, GCSFR, PRTN3 and CLC. We also detected over-expression of S100A12, expressed in nerve cells but also in myeloid cells. In addition to the myeloid-specific genes, other over-expressed genes included AML1, LCP2 and FGF6. In conclusion, our study revealed novel information about gene expression in childhood ALL. The data obtained may contribute to further studies of the pathogenesis and prognosis of childhood ALL.

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References

  1. Ma SK, Wan TS, Chan LC . Cytogenetics and molecular genetics of childhood leukemia Hematol Oncol 1999 17: 91–105

    Article  CAS  PubMed  Google Scholar 

  2. Schrappe M, Camitta B, Pui CH, Eden T, Gaynon P, Gustafsson G, Janka-Schaub GE, Kamps W, Masera G, Sallan S, Tsuchida M, Vilmer E . Long-term results of large prospective trials in childhood acute lymphoblastic leukemia Leukemia 2000 14: 2193–2194

    Article  CAS  PubMed  Google Scholar 

  3. Gustafsson G, Kreuger A, Clausen N, Garwicz S, Kristinsson J, Lie SO, Moe PJ, Perkkiö M, Yssing M, Saarinen-Pihkala UM . Intensified treatment of acute childhood lymphoblastic leukaemia has improved prognosis, especially in non-high-risk patients: the Nordic experience of 2648 patients diagnosed between 1981 and 1996. Nordic Society of Paediatric Haematology and Oncology (NOPHO) Acta Paediatr 1998 87: 1151–1161

    Article  CAS  PubMed  Google Scholar 

  4. Hilsenbeck SG, Friedrichs WE, Schiff R, O'Connell P, Hansen RK, Osborne CK, Fuqua SA . Statistical analysis of array expression data as applied to the problem of tamoxifen resistance J Natl Cancer Inst 1999 91: 453–459

    Article  CAS  PubMed  Google Scholar 

  5. Swets JA . Measuring the accuracy of diagnostic systems Science 1988 240: 1285–1293

    Article  CAS  PubMed  Google Scholar 

  6. Hanley JA, McNeil BJ . The meaning and use of the area under a receiver operating characteristic (ROC) curve Radiology 1982 143: 29–36

    CAS  PubMed  Google Scholar 

  7. Good P . Permutation Tests – a Practical Guide to Resampling Methods for Testing Hypothesis, 2nd edn Springer Verlag: New York 2000

    Google Scholar 

  8. Yeoh E-J, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, Behm FG, Raimondi SC, Relling MV, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Li J, Liu H, Pui C-H, Evans WE, Naeve C, Wong L, Downing JR . Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling Cancer Cell 2002 1: 133–143

    Article  CAS  PubMed  Google Scholar 

  9. Hamaguchi H, Yamada M, Noguchi A, Fujii K, Shibasaki M, Mukai R, Yabe T, Kondo I . Genetic analysis of human lymphocyte proteins by two-dimensional gel electrophoresis: 2. Genetic polymorphism of lymphocyte cytosol 64K polypeptide Hum Genet 1982 60: 176–180

    Article  CAS  PubMed  Google Scholar 

  10. Zhou LJ, Schwarting R, Smith HM, Tedder TF . A novel cell-surface molecule expressed by human interdigitating reticulum cells, Langerhans cells, and activated lymphocytes is a new member of the Ig superfamily J Immunol 1992 149: 735–742

    CAS  PubMed  Google Scholar 

  11. Hibbs ML, Dunn AR . Lyn, a src-like tyrosine kinase Int J Biochem Cell Biol 1997 29: 397–400

    Article  CAS  PubMed  Google Scholar 

  12. Su GH, Ip HS, Cobb BS, Lu MM, Chen HM, Simon MC . The Ets protein Spi-B is expressed exclusively in B cells and T cells during development J Exp Med 1996 184: 203–214

    Article  CAS  PubMed  Google Scholar 

  13. Yokoyama S, Staunton D, Fisher R, Amiot M, Fortin JJ, Thorley-Lawson DA . Expression of the Blast-1 activation/adhesion molecule and its identification as CD48 J Immunol 1991 146: 2192–2200

    CAS  PubMed  Google Scholar 

  14. Nagata S, Fukunaga R . Granulocyte colony-stimulating factor and its receptor Prog Growth Factor Res 1991 3: 131–141

    Article  CAS  PubMed  Google Scholar 

  15. Bories D, Raynal MC, Solomon DH, Darzynkiewicz Z, Cayre YE . Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells Cell 1989 59: 959–968

    Article  CAS  PubMed  Google Scholar 

  16. Rosenberg HF . The eosinophil ribonucleases Cell Mol Life Sci 1998 54: 795–803

    Article  CAS  PubMed  Google Scholar 

  17. Weller PF, Bach D, Austen KF . Human eosinophil lysophospholipase: the sole protein component of Charcot-Leyden crystals J Immunol 1982 128: 1346–1349

    CAS  PubMed  Google Scholar 

  18. Pui CH, Raimondi SC, Head DR, Schell MJ, Rivera GK, Mirro J Jr, Crist WM, Behm FG . Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse Blood 1991 78: 1327–1337

    CAS  PubMed  Google Scholar 

  19. Suda T, Suda J, Kajigaya S, Nagata S, Asano S, Saito M, Miura Y . Effects of recombinant murine granulocyte colony-stimulating factor on granulocyte–macrophage and blast colony formation Exp Hematol 1987 15: 958–965

    CAS  PubMed  Google Scholar 

  20. de Lau WB, Hurenkamp J, Berendes P, Touw IP, Clevers HC, van Dijk MA . The gene encoding the granulocyte colony-stimulating factor receptor is a target for deregulation in pre-B ALL by the t(1;19)-specific oncoprotein E2A-Pbx1 Oncogene 1998 17: 503–510

    Article  CAS  PubMed  Google Scholar 

  21. Lutz PG, Moog-Lutz C, Coumau-Gatbois E, Kobari L, Di Gioia Y, Cayre YE . Myeloblastin is a granulocyte colony-stimulating factor-responsive gene conferring factor-independent growth to hematopoietic cells Proc Natl Acad Sci USA 2000 97: 1601–1606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bjurholm A, Kreicbergs A, Brodin E, Schultzberg M . Substance P- and CGRP-immunoreactive nerves in bone Peptides 1988 9: 165–171

    Article  CAS  PubMed  Google Scholar 

  23. Guignard F, Mauel J, Markert M . Identification and characterization of a novel human neutrophil protein related to the S100 family Biochem J 1995 309: 395–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Robinson MJ, Hogg N . A comparison of human S100A12 with MRP-14 (S100A9) Biochem Biophys Res Commun 2000 275: 865–870

    Article  CAS  PubMed  Google Scholar 

  25. Fernandez S, Knopf MA, McGillis JP . Calcitonin-gene related peptide (CGRP) inhibits interleukin-7-induced pre-B cell colony formation J Leukoc Biol 2000 67: 669–676

    Article  CAS  PubMed  Google Scholar 

  26. Aalto Y, El-Rifai W, Vilpo L, Ollila J, Nagy B, Vihinen M, Vilpo J, Knuutila S . Distinct gene expression profiling in chronic lymphocytic leukemia with 11q23 deletion Leukemia 2001 15: 1721–1728

    Article  CAS  PubMed  Google Scholar 

  27. Anderson MK, Hernandez-Hoyos G, Diamond RA, Rothenberg EV . Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage Development 1999 126: 3131–3148

    CAS  PubMed  Google Scholar 

  28. Baskaran K, Erfurth F, Taborn G, Copeland NG, Gilbert DJ, Jenkins NA, Iannaccone PM, Domer PH . Cloning and developmental expression of the murine homolog of the acute leukemia proto-oncogene AF4 Oncogene 1997 15: 1967–1978

    Article  CAS  PubMed  Google Scholar 

  29. Heim S, Mitelman F . Cancer Cytogenetics, 2nd edn Wiley-Liss: New York 1995

    Google Scholar 

  30. Golub TR, Barker GF, Bohlander SK, Hiebert SW, Ward DC, Bray-Ward P, Morgan E, Raimondi SC, Rowley JD, Gilliland DG . Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia Proc Natl Acad Sci USA 1995 92: 4917–4921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Romana SP, Mauchauffé M, Le Coniat M, Chumakov I, Le Paslier D, Berger R, Bernard OA . The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion Blood 1995 85: 3662–3670

    CAS  PubMed  Google Scholar 

  32. Larsson LG, Schena M, Carlsson M, Sällströöm J, Nilsson K . Expression of the c-myc protein is down-regulated at the terminal stages during in vitro differentiation of B-type chronic lymphocytic leukemia cells Blood 1991 77: 1025–1032

    CAS  PubMed  Google Scholar 

  33. Erikson J, Finger L, Sun L, ar-Rushdi A, Nishikura K, Minowada J, Finan J, Emanuel BS, Nowell PC, Croce CM . Deregulation of c-myc by translocation of the alpha-locus of the T-cell receptor in T-cell leukemias Science 1986 232: 884–886

    Article  CAS  PubMed  Google Scholar 

  34. Alitalo K, Saksela K, Winqvist R, Alitalo R, Keski-Oja J, Laiho M, Ilvonen M, Knuutila S, de la Chapelle A . Acute myelogenous leukaemia with c-myc amplification and double minute chromosomes Lancet 1985 2: 1035–1039

    Article  CAS  PubMed  Google Scholar 

  35. Preisler HD, Kinniburgh AJ, Wei-Dong G, Khan S . Expression of the protooncogenes c-myc, c-fos, and c-fms in acute myelocytic leukemia at diagnosis and in remission Cancer Res 1987 47: 874–880

    CAS  PubMed  Google Scholar 

  36. Baer MR, Augustinos P, Kinniburgh AJ . Defective c-myc and c-myb RNA turnover in acute myeloid leukemia cells Blood 1992 79: 1319–1326

    CAS  PubMed  Google Scholar 

  37. Romana SP, Poirel H, Leconiat M, Flexor MA, Mauchauffe M, Jonveaux P, Macintyre EA, Berger R, Bernard OA . High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia Blood 1995 86: 4263–4269

    CAS  PubMed  Google Scholar 

  38. Shurtleff SA, Buijs A, Behm FG, Rubnitz JE, Raimondi SC, Hancock ML, Chan GC, Pui CH, Grosveld G, Downing JR . TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis Leukemia 1995 9: 1985–1989

    CAS  PubMed  Google Scholar 

  39. Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi MG, Ludwig WD, Burci L, Mangioni S, Schrappe M, Riehm H, Lampert F, Basso G, Masera G, Harbott J, Biondi A . Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin–Frankfurt–Munster Study Group Blood 1997 90: 571–577

    CAS  PubMed  Google Scholar 

  40. Niini T, Kanerva J, Vettenranta K, Saarinen-Pihkala UM, Knuutila S . AML1 gene amplification: a novel finding in childhood acute lymphoblastic leukemia Haematologica 2000 85: 362–366

    CAS  PubMed  Google Scholar 

  41. Larramendy ML, Huhta T, Vettenranta K, El-Rifai W, Lundin J, Pakkala S, Saarinen-Pihkala UM, Knuutila S . Comparative genomic hybridization in childhood acute lymphoblastic leukemia Leukemia 1998 12: 1638–1644

    Article  CAS  PubMed  Google Scholar 

  42. Strom DK, Nip J, Westendorf JJ, Linggi B, Lutterbach B, Downing JR, Lenny N, Hiebert SW . Expression of the AML-1 oncogene shortens the G(1) phase of the cell cycle J Biol Chem 2000 275: 3438–3445

    Article  CAS  PubMed  Google Scholar 

  43. Kurokawa M, Tanaka T, Tanaka K, Ogawa S, Mitani K, Yazaki Y, Hirai H . Overexpression of the AML1 proto-oncoprotein in NIH3T3 cells leads to neoplastic transformation depending on the DNA-binding and transactivational potencies Oncogene 1996 12: 883–892

    CAS  PubMed  Google Scholar 

  44. Miyoshi H, Ohira M, Shimizu K, Mitani K, Hirai H, Imai T, Yokoyama K, Soeda E, Ohki M . Alternative splicing and genomic structure of the AML1 gene involved in acute myeloid leukemia Nucleic Acids Res 1995 23: 2762–2769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Levanon D, Glusman G, Bangsow T, Ben-Asher E, Male DA, Avidan N, Bangsow C, Hattori M, Taylor TD, Taudien S, Blechschmidt K, Shimizu N, Rosenthal A, Sakaki Y, Lancet D, Groner Y . Architecture and anatomy of the genomic locus encoding the human leukemia-associated transcription factor RUNX1/AML1 Gene 2001 262: 23–33

    Article  CAS  PubMed  Google Scholar 

  46. Rudd CE . Lymphocyte signaling: adapting new adaptors Curr Biol 1998 8: R805–R808

    Article  CAS  PubMed  Google Scholar 

  47. Jackman JK, Motto DG, Sun Q, Tanemoto M, Turck CW, Peltz GA, Koretzky GA, Findell PR . Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells J Biol Chem 1995 270: 7029–7032

    Article  CAS  PubMed  Google Scholar 

  48. Mizuno K, Katagiri T, Hasegawa K, Ogimoto M, Yakura H . Hematopoietic cell phosphatase, SHP-1, is constitutively associated with the SH2 domain-containing leukocyte protein, SLP-76, in B cells J Exp Med 1996 184: 457–463

    Article  CAS  PubMed  Google Scholar 

  49. Nakayama Y, Iwamoto Y, Maher SE, Tanaka Y, Bothwell AL . Altered gene expression upon BCR cross-linking in Burkitt's lymphoma B cell line Biochem Biophys Res Commun 2000 277: 124–127

    Article  CAS  PubMed  Google Scholar 

  50. Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M . Receptor specificity of the fibroblast growth factor family J Biol Chem 1996 271: 15292–15297

    Article  CAS  PubMed  Google Scholar 

  51. Allouche M, Bayard F, Clamens S, Fillola G, Sié P, Amalric F . Expression of basic fibroblast growth factor (bFGF) and FGF-receptors in human leukemic cells Leukemia 1995 9: 77–86

    CAS  PubMed  Google Scholar 

  52. Bikfalvi A, Han ZC, Fuhrmann G . Interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis and demonstration of FGF receptor expression in megakaryocytes and megakaryocytic-like cells Blood 1992 80: 1905–1913

    CAS  PubMed  Google Scholar 

  53. Pizette S, Coulier F, Birnbaum D, DeLapeyrière O . FGF6 modulates the expression of fibroblast growth factor receptors and myogenic genes in muscle cells Exp Cell Res 1996 224: 143–151

    Article  CAS  PubMed  Google Scholar 

  54. Popovici C, Adélaïde J, Ollendorff V, Chaffanet M, Guasch G, Jacrot M, Leroux D, Birnbaum D, Pébusque MJ . Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13) Proc Natl Acad Sci USA 1998 95: 5712–5717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Popovici C, Zhang B, Grégoire MJ, Jonveaux P, Lafage-Pochitaloff M, Birnbaum D, Pébusque MJ . The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1 Blood 1999 93: 1381–1389

    CAS  PubMed  Google Scholar 

  56. Guasch G, Mack GJ, Popovici C, Dastugue N, Birnbaum D, Rattner JB, Pébusque MJ . FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33) Blood 2000 95: 1788–1796

    CAS  PubMed  Google Scholar 

  57. Larramendy ML, Niini T, Elonen E, Nagy B, Ollila J, Vihinen M, Knuutila S . Overexpression of translocation-associated fusion genes of FGFR1, MYC, NPMI, and DEK, but absence of translocations in acute myeloid leukemia. A microarray analysis Haematologica 2002 87: 569–577

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the Finnish Cancer Institution Foundation, Nona and Kullervo Väre Foundation, Biomedicum Helsinki Foundation, Sigrid Juselius Foundation and the research funds of Helsinki University Central Hospital, in Finland.

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Authors and Affiliations

  1. Departments of Pathology and Medical Genetics, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Finland

    T Niini, ML Larramendy, Y Aalto, H Wikman, B Nagy, A Ferrer Salvador & S Knuutila

  2. Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland

    K Vettenranta & UM Saarinen-Pihkala

  3. Laboratory of Computer and Information Science, Helsinki University of Technology, Espoo, Finland

    J Hollmén, JK Seppänen & H Mannila

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Niini, T., Vettenranta, K., Hollmén, J. et al. Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia – a cDNA array study. Leukemia 16, 2213–2221 (2002). https://doi.org/10.1038/sj.leu.2402685

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