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Clinical Laboratory Correlates

Characterization of acute myeloid leukemia with MLL rearrangements – no increase in the incidence of coexpression of lymphoid-associated antigens on leukemic blasts

Leukemia volume 14, pages 1025–1030 (2000)Cite this article

Abstract

MLL gene rearrangements are associated with coexpression of myeloid- and lymphoid-associated antigens on leukemic blasts and a dismal outcome in acute lymphoblastic leukemia (ALL). Whether the same conditions can apply to acute myeloid leukemia (AML) is not quite clear. Rearrangements of the MLL gene were analyzed on 113 patients with newly diagnosed de novo AML in a single institution. Sixteen (14%) of them showed rearranged bands by Southern blot analysis, including three (50%) of six infants, three (14%) of 21 children between 1 and 15 years and 10 (12%) of 86 adults. MLL rearrangements were not only detected in M5 (four of 12 patients, 33%) and M4 (six of 31, 19%) subtypes but also in other non-M4–M5 AML (six of 70, 9%), including M1, M2 and M7, but not M3 subtype. Seven patients had chromosomal abnormalities involving 11q23, but nine did not. The latter comprised three (6%) of 48 patients with normal karyotype, one with t(8;21), none with t(15;17), inv(16) or t(9;22), and four (15%) of 27 with cytogenetic aberrations other than those specific structural abnormalities. In contrast to ALL, AML patients with MLL rearrangements did not tend to coexpress lymphoid- and myeloid-associated antigens simultaneously on leukemic blasts and have similar outcome as those without the gene rearrangements.

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References

  1. Mrozek K, Heinonen K, de la Chapelle A, Bloomfield CD . Clinical significance of cytogenetics in acute myeloid leukemia Semin Oncol 1997 24: 17–31

    CAS  PubMed  Google Scholar 

  2. Rabbits TH . Chromosomal translocation in human cancer Nature 1994 372: 143–149

    Article  Google Scholar 

  3. Heim S, Mitelman F . Cancer Cytogenetics Wiley-Liss: New York 1995

    Google Scholar 

  4. Rowley JD . Rearrangements involving chromosome band 11q23 in acute leukemia Semin Cancer 1993 4: 377–385

    CAS  Google Scholar 

  5. Ziemin-van der Poel S, McCabe NR, Gill HJ, Espinosa III R, Patel YD, Harden AM, Le Beau MM, Smith SB, Rowley JD, Diaz MO . Identification of a gene (MLL) which spans the breakpoint in 11q23 translocations associated with human leukemias Proc Natl Acad Sci USA 1991 88: 10735–10739

    Article  CAS  Google Scholar 

  6. Cimino G, Moir DT, Canaani O, Williams K, Crist WM, Katzav S, Cannizaro L, Lange B, Nowell PC, Croce CM, Canaani E . Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations Cancer Res 1991 51: 6712–6714

    CAS  PubMed  Google Scholar 

  7. Tkachuk DC, Kohler S, Cleary ML . Involvement of a homolog of drosophila trithorax by 11q23 chromosomal translocations in acute leukemias Cell 1992 71: 691–700

    Article  CAS  Google Scholar 

  8. Djabali M, Selleri L, Parry P, Bower M, Young BD, Evans GA . A trithorax like gene is interrupted by chromosome 11q23 translocations in acute leukemias Nat Genet 1992 2: 113–118

    Article  CAS  Google Scholar 

  9. Bernard OA, Berger R . Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations Genes Chromos Cancer 1995 13: 75–85

    Article  CAS  Google Scholar 

  10. Rowley JD . Seminars from the University of Minnesota. Chromosome translocations: dangerous liaisons J Lab Clin Med 1998 132: 244–250

    Article  CAS  Google Scholar 

  11. Rubnitz JE, Behm FG, Downing JR . 11q23 rearrangements in acute leukemia Leukemia 1996 10: 74–82

    CAS  PubMed  Google Scholar 

  12. Thirman MJ, Gill HJ, Burnett RC, Mbangkollo D, McCabe NR, Kobayashi H, Ziemin-van der Poel, Kaneko Y, Morgan R, Sadberg AA, Chaganti RSK, Larson RA, Le Beau MM, Diaz MO, Rowley JD . Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations New Engl J Med 1993 329: 909–914

    Article  CAS  Google Scholar 

  13. Raimondi SC, Frestedt JL, Pui CH, Downing JR, Head DR, Kersey JH, Behm FG . Acute lymphoblastic leukemia with deletion of 11q23 or a novel inversion(11)(p13q23) lack MLL gene rearrangements and have favorable clinical features Blood 1995 86: 1881–1886

    CAS  PubMed  Google Scholar 

  14. Kobayashi H, Espinosa III R, Thirman MJ, Gill HJ, Fernald AA, Diaz MO, Le Beau MM, Rowley JD . Heterogeneity of breakpoints of 11q23 rearrangements in hematologic malignancies identified with fluorescence in situ hybridization Blood 1993 82: 547–551

    CAS  PubMed  Google Scholar 

  15. Bower M, Parry P, Carter M, Lillington DM, Amess J, Lister TA, Evans G, Young BD . Prevalence and clinical correlations of MLL gene rearrangements in AML-M4/M5 Blood 1994 84: 3776–3780

    CAS  PubMed  Google Scholar 

  16. Lo Coco F, Mandelli F, Breccia M, Annino L, Guglielmi C, Petti MC, Testi AM, Alimena G, Croce CM, Canaani E, Cimino G . Southern blot analysis of ALL-1 rearrangements at chromosome 11q23 in acute leukemia Cancer Res 1993 53: 3800–3803

    CAS  PubMed  Google Scholar 

  17. Cimino G, Rapanotti MC, Elia L, Biondi A, Fizzotti M, Testi AM, Tosti S, Croce CM, Canaani E, Mandelli F, Lo Coco F . ALL-1 gene rearrangements in acute myeloid leukemia: association with M4–M5 French–American–British classification subtypes and young age Cancer Res 1995 55: 1625–1628

    CAS  PubMed  Google Scholar 

  18. Behm FG, Raimondi SC, Frestedt JL, Liu Q, Crist JR, Downing JR, Rivera GK, Kersey JH, Pui CH . Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age Blood 1996 87: 2870–2877

    CAS  PubMed  Google Scholar 

  19. Chen CS, Sorensen PHB, Domer PH, Reaman GH, Korsmeyer SJ, Heerema NA, Hammond GD, Kersey JH . Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome Blood 1993 81: 2386–2393

    CAS  PubMed  Google Scholar 

  20. Archimbaud D, Charrin C, Magand JP, Campos L, Thomas X, Fiere D, Rimokh R . Clinical and biological characteristics of adult de novo and secondary acute myeloid leukemia with balanced 11q23 chromosomal anomaly or MLL gene rearrangement compared to case with unbalanced 11q23 anomaly: confirmation of the existence of different entities with 11q23 breakpoint Leukemia 1998 12: 25–33

    Article  CAS  Google Scholar 

  21. Bennet JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C . Proposed revised criteria for the classification of acute myeloid leukemias. A report of the French–American–British Cooperative Group Ann Intern Med 1985 103: 626–629

    Article  Google Scholar 

  22. Bennet JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C . Criteria for the diagnosis of acute leukemia of megakaryocytic lineage (M7): a report of the French–American–British Cooperative Group Ann Intern Med 1985 103: 460–462

    Article  Google Scholar 

  23. Tien HF, Wang CH, Lin MT, Lee FY, Liu MC, Chuang SM, Chen YC, Shen MC, Lin KH, Zin DT . Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia Cancer Genet Cytogenet 1995 84: 60–68

    Article  CAS  Google Scholar 

  24. Mitelman F (ed) . ISCN (1995). An International System for Human Cytogenetic Nomenclature S Karger: Basel

  25. Tien HF, Wang CH, Chen YC, Shen MC, Lin DT, Lin KH . Characterization of acute myeloid leukemia (AML) coexpressing lymphoid markers: different biologic features between T cell antigen positive and B cell antigen positive AML Leukemia 1993 7: 688–695

    CAS  PubMed  Google Scholar 

  26. Tien HF, Wang CH, Su IJ, Wu HS, Chien SH, Chen YC, Lin DT, Lin KH, Shen MC . Immunoglobulin and T cell receptor gene rearrangements in acute lymphoblastic leukemia – a higher incidence of double rearrangements in patients with myeloid antigen expression Leukemia Res 1991 15: 91–98

    Article  CAS  Google Scholar 

  27. Aplan PD, Chervinsky DS, Stanulla M . Site-specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitor Blood 1996 87: 2649–2658

    CAS  PubMed  Google Scholar 

  28. Stanulla M, Wang J, Chervinsky DS, Thandla S, Aplan PD . DNA cleavage within the MLL breakpoint cluster region is a specific event which occurs as part of higher-order chromatin fragmentation during the initial stages of apoptosis Mol Cell Biol 1997 17: 4070–4079

    Article  CAS  Google Scholar 

  29. Stanulla M, Schunemann HJ, Thandla S, Brecher ML, Aplan PD . Pseudo-rearrangement of the MLL gene at chromosome 11q23: a cautionary note on genotype analysis of leukaemia patients J Clin Pathol Mol Pathol 1998 51: 85–89

    Article  CAS  Google Scholar 

  30. Rubnitz JE, Link MP, Shuster JJ, Carroll AJ, Hakami N, Frankel LS, Pullen DJ, Cleary ML . Frequency and prognostic significance of HRX rearrangements in infant acute lymphoblastic leukemia: a Pediatric Oncology Group Study Blood 1994 84: 570–573

    CAS  PubMed  Google Scholar 

  31. Poirel H, Rack K, Delabesse E, Radford-Weiss I, Troussard X, Debert C, Laboeuf D, Bastard C, Picard F, Veil-Buzyn A, Flandrin G, Bernard O, Macintyre E . Incidence and characterization of MLL gene (11q23) rearrangements in acute myeloid leukemia M1 and M5 Blood 1996 87: 2496–2505

    CAS  PubMed  Google Scholar 

  32. Macintyre E, Bourquelot P, Leboeuf D, Rimokh R, Archimbaud D, Smetsers T, Zittoun R . MLL cleavage occurs in approximately 5% of de novo acute myeloid leukemia, including in patients analyzed before treatment induction Blood 1997 89: 2224–2226

    CAS  PubMed  Google Scholar 

  33. Schichman SA, Caligiuri MA, Strout MP, Carter SL, Gu Y, Canaani E, Bloomfield CD, Croce CM . ALL-1 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements Cancer Res 1994 54: 4277–4280

    CAS  PubMed  Google Scholar 

  34. Yu M, Honoki K, Anderson J, Paietta E, Nam DK, Yunis JJ . MLL tandem duplication and multiple splicing in adult acute myeloid leukemia with normal karyotype Leukemia 1996 10: 774–780

    CAS  PubMed  Google Scholar 

  35. Caligiuri MA, Strout MP, Schichman SA, Mrozek K, Arthur DC, Herzig GP, Baer MR, Schiffer CA, Heinonen K, Knuutila S, Nousiainen T, Ruutu T, Block AW, Schulman P, Pedersen-Bjergaard J, Croce CM, Bloomfield CD . Partial tandem duplication of ALL as a recurrent molecular defect in acute myeloid leukemia with trisomy 11 Cancer Res 1996 56: 1418–1425

    CAS  PubMed  Google Scholar 

  36. Caligiuri MA, Strout MP, Lawrence D, Arthur DC, Baer MR, Yu F, Knuutila S, Mrozek K, Oberkircher AR, Marcucci G, de la Chapelle A, Elonen E, Block AW, Rao PN, Herzig GP, Powell BL, Ruutu T, Schiffer CA, Bloomfield CD . Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics Cancer Res 1998 58: 55–59

    CAS  PubMed  Google Scholar 

  37. Ball ED, Davis RB, Griffin JD, Mayer RJ, Davery FR, Arthur DC, Wurster-Hill D, Noll W, Elghetany MT, Allen SL, Rai K, Lee EJ, Schiffer CA, Bloomfield CD . Prognostic value of lymphocyte surface markers in acute myeloid leukemia Blood 1991 77: 2242–2250

    CAS  PubMed  Google Scholar 

  38. Marosi C, Koller U, Koller-Weber E, Schwarzinger I, Jager U, Vahls P, Nowotny H, Pirc-Danoewinata H, Steger G, Kreiner G, Wagner B, Lechner K, Lutz D, Bettelheim P, Haas OA . Prognostic impact of karyotype and immunologic phenotype in 125 adult patients with de novo AML Cancer Genet Cytogenet 1992 64: 14–25

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported in part by grants from the National Science Council of the Republic of China, NSC 87-2314-B002-074 and the Children Cancer Foundation of the Republic of China, 85-11 and 86-15.

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Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    H-F Tien, C-H Hsiao, J-L Tang, W Tsay, C-H Hu, Y-Y Kuo, C-H Wang, Y-C Chen & M-C Shen

  2. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

    C-H Wang, Y-C Chen, M-C Shen & D-T Lin

  3. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

    D-T Lin, K-H Lin & K-S Lin

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Tien, HF., Hsiao, CH., Tang, JL. et al. Characterization of acute myeloid leukemia with MLL rearrangements – no increase in the incidence of coexpression of lymphoid-associated antigens on leukemic blasts. Leukemia 14, 1025–1030 (2000). https://doi.org/10.1038/sj.leu.2401791

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