Current Oncology Reports

, Volume 9, Issue 5, pp 373–377 | Cite as

Therapy-related acute myelogenous leukemia and myelodysplastic syndrome

Article

Abstract

Therapy-related acute myelogenous leukemia and myelodysplastic syndrome (t-AML/MDS) are increasing in prevalence with aging of the population and improved survival of patients treated with chemotherapy or radiotherapy for other malignancies. Research focused on the pathogenesis of t-AML/MDS will provide insight into the pathogenesis of de novo AML/MDS. Participation in clinical trials should be encouraged for this patient population because results with available treatment options are clearly suboptimal.

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References and Recommended Reading

  1. 1.
    Mauritzson N, Albin M, Rylander L, et al.: Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001. Leukemia 2002, 16:2366–2378.PubMedCrossRefGoogle Scholar
  2. 2.
    Pedersen-Bjergaard J, Specht L, Larsen SO, et al.: Risk of therapy-related leukaemia and preleukaemia after Hodgkin’s disease: relation to age, cumulative dose of alkylating agents, and time from chemotherapy. Lancet 1987, ii:83–88.CrossRefGoogle Scholar
  3. 3.
    Pui CH, Behm FG, Raimondi SC, et al.: Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia. N Engl J Med 1989, 321:136–142.PubMedCrossRefGoogle Scholar
  4. 4.
    Pedersen-Bjergaard J, Larsen SO: Incidence of acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome up to 10 years after treatment of Hodgkin’s disease. N Engl J Med 1982, 307:965–971.PubMedCrossRefGoogle Scholar
  5. 5.
    Hake CR, Graubert TA, Fenske TS: Dose autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients? Bone Marrow Transplant 2007, 39:59–70.PubMedCrossRefGoogle Scholar
  6. 6.
    Oosterveld M, Muus P, Suciu S, et al.: Chemotherapy only compared to chemotherapy followed by transplantation in high risk myelodysplastic syndrome and secondary acute myeloid leukemia, two parallel studies adjusted for various prognostic factors. Leukemia 2002, 16:1615–1621.PubMedCrossRefGoogle Scholar
  7. 7.
    Pedersen-Bjergaard J, Andersen MK, Christiansen DH: Therapy-related acute myeloid leukemia and myelodysplasia after high-dose chemotherapy and autologous stem cell transplantation. Blood 2000, 95:3273–3279.PubMedGoogle Scholar
  8. 8.
    Berk PD, Goldberg JD, Silverstein MN, et al.: Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med 1981, 304:441–447.PubMedCrossRefGoogle Scholar
  9. 9.
    Boice JD Jr, Greene MH, Killen JY Jr, et al.: Leukemia and preleukemia after adjuvant treatment of gastrointestinal cancer with semustine (methyl-CCNU). N Engl J Med 1983, 309:1079–1084.PubMedCrossRefGoogle Scholar
  10. 10.
    Kyle RA, Pierre RV, Bayrd ED: Multiple myeloma and acute myelomonocytic leukemia. N Engl J Med 1970, 283:1121–1125.PubMedCrossRefGoogle Scholar
  11. 11.
    Reimer RR, Hoover R, Fraumeni JF Jr, Young RC: Acute leukemia after alkylating-agent therapy of ovarian cancer. N Engl J Med 1977, 297:177–181.PubMedCrossRefGoogle Scholar
  12. 12.
    Cremin P, Flattery M, McCann SR, Daly PA: Myelodysplasia and acute myeloid leukaemia following adjuvant chemotherapy for breast cancer using mitoxantrone and methotrexate with or without mitomycin. Ann Oncol 1996, 7:745–746.PubMedGoogle Scholar
  13. 13.
    Pedersen-Bjergaard J, Daugaard G, et al.: Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Lancet 1991, 338:359–363.PubMedCrossRefGoogle Scholar
  14. 14.
    Ratain MJ, Kaminer LS, Bitran JD, et al.: Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung. Blood 1987, 70:1412–1417.PubMedGoogle Scholar
  15. 15.
    Felix CA, Lange BJ, Hosler MR, et al.: Chromosome band 11q23 translocation breakpoints are DNA topoisomerase II cleavage sites. Cancer Res 1995, 55:4287–4292.PubMedGoogle Scholar
  16. 16.
    Stanulla M, Wang J, Chervinsky DS, et al.: 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.PubMedGoogle Scholar
  17. 17.
    Stanulla M, Chhalliyil P, Wang J, et al.: Mechanisms of MLL gene rearrangement: site-specific DNA cleavage within the breakpoint cluster region is independent of chromosomal context. Hum Mol Genet 2001, 10:2481–2491.PubMedCrossRefGoogle Scholar
  18. 18.
    Mistry AR, Felix CA, Whitmarsh RJ, et al.: DNA topoisomerase II in therapy-related acute promyelocytic leukemia. N Engl J Med 2005, 352:1529–1538.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang Y, Strissel P, Strick R, et al.: Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8,21) leukemia. Proc Natl Acad Sci U S A 2002, 99:3070–3075.PubMedCrossRefGoogle Scholar
  20. 20.
    Frohling S, Scholl C, Gilliland DG, Levine RL: Genetics of myeloid malignancies: pathogenetic and clinical implications. J Clin Oncol 2005, 23:6285–6295.PubMedCrossRefGoogle Scholar
  21. 21.
    Gilliland DG, Jordan CT, Felix CA: The molecular basis of leukemia. Hematology Am Soc Hematol Educ Program 2004, 80–97.Google Scholar
  22. 22.
    Pedersen-Bjergaard J, Christiansen DH, Andersen MK, Skovby F: Causality of myelodysplasia and acute myeloid leukemia and their genetic abnormalities. Leukemia 2002, 16:2177–2184.PubMedCrossRefGoogle Scholar
  23. 23.
    Pedersen-Bjergaard J, Christiansen DH, Desta F, Andersen MK: Alternative genetic pathways and cooperating genetic abnormalities in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 2006, 20:1943–1949.PubMedCrossRefGoogle Scholar
  24. 24.
    Christiansen DH, Andersen MK, Desta F, Pedersen-Bjergaard J: Mutations of genes in the receptor tyrosine kinase (RTK)/RAS-BRAF signal transduction pathway in therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 2005, 19:2232–2240.PubMedCrossRefGoogle Scholar
  25. 25.
    Christiansen DH, Andersen MK, Pedersen-Bjergaard J: Methylation of p15INK4B is common, is associated with deletion of genes on chromosome arm 7q and predicts a poor prognosis in therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 2003, 17:1813–1819.PubMedCrossRefGoogle Scholar
  26. 26.
    Andersen MK, Christiansen DH, Kirchhoff M, Pedersen-Bjergaard J: Duplication or amplification of chromosome band 11q23, including the unrearranged MLL gene, is a recurrent abnormality in therapy-related MDS and AML, and is closely related to mutation of the TP53 gene and to previous therapy with alkylating agents. Genes Chromosomes Cancer 2001, 31:33–41.PubMedCrossRefGoogle Scholar
  27. 27.
    Christiansen DH, Andersen MK, Pedersen-Bjergaard J: Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 2001, 19:1405–1413.PubMedGoogle Scholar
  28. 28.
    Roddam PL, Rollinson S, Kane E, et al.: Poor metabolizers at the cytochrome P450 2D6 and 2C19 loci are at increased risk of developing adult acute leukaemia. Pharmacogenetics 2000, 10:605–615.PubMedCrossRefGoogle Scholar
  29. 29.
    Bolufer P, Collado M, Barragan E, et al.: Profile of polymorphisms of drug-metabolising enzymes and the risk of therapy-related leukaemia. Br J Haematol 2007, 136:590–596.PubMedCrossRefGoogle Scholar
  30. 30.
    Fern L, Pallis M, Ian CG, Seedhouse C, et al.: Clonal haemopoiesis may occur after conventional chemotherapy and is associated with accelerated telomere shortening and defects in the NQO1 pathway, possible mechanisms leading to an increased risk of t-AML/MDS. Br J Haematol 2004, 126:63–71.PubMedCrossRefGoogle Scholar
  31. 31.
    Jawad M, Seedhouse CH, Russell N, Plumb M: Polymorphisms in human homeobox HLX1 and DNA repair RAD51 genes increase the risk of therapy-related acute myeloid leukemia. Blood 2006, 108:3916–3918.PubMedCrossRefGoogle Scholar
  32. 32.
    Seedhouse C, Faulkner R, Ashraf N, et al.: Polymorphisms in genes involved in homologous recombination repair interact to increase the risk of developing acute myeloid leukemia. Clin Cancer Res 2004, 10:2675–2680.PubMedCrossRefGoogle Scholar
  33. 33.
    Gardin C, Chaibi P, de Revel T, et al.: Intensive chemotherapy with idarubicin, cytosine arabinoside, and granulocyte colony-stimulating factor (G-CSF) in patients with secondary and therapy-related acute myelogenous leukemia. Club de Reflexion en Hematologie. Leukemia 1997, 11:16–21.PubMedCrossRefGoogle Scholar
  34. 34.
    Oosterveld M, Suciu S, Verhoef G, et al.: The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921). Leukemia 2003, 17:859–868.PubMedCrossRefGoogle Scholar
  35. 35.
    Pagano L, Pulsoni A, Vignetti M, et al.: Secondary acute myeloid leukaemia: results of conventional treatments. Experience of GIMEMA trials. Ann Oncol 2005, 16:228–233.PubMedCrossRefGoogle Scholar
  36. 36.
    Damiani D, Michieli M, Ermacora A, et al.: P-glycoprotein (PGP), and not lung resistance-related protein (LRP), is a negative prognostic factor in secondary leukemias. Haematologica 1998, 83:290–297.PubMedGoogle Scholar
  37. 37.
    Rund D, Krichevsky S, Bar-Cohen S, et al.: Therapy-related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients. Leukemia 2005, 19:1919–1928.PubMedCrossRefGoogle Scholar
  38. 38.
    Andersen MK, Larson RA, Mauritzson N, et al.: Balanced chromosome abnormalities inv(16) and t(15,17) in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop. Genes Chromosomes Cancer 2002, 33:395–400.PubMedCrossRefGoogle Scholar
  39. 39.
    Schnittger S, Bacher U, Haferlach C, et al.: Rare CBFBMYH11 fusion transcripts in AML with inv(16)/t(16,16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients. Leukemia 2007, 21:725–731.PubMedGoogle Scholar
  40. 40.
    Pedersen-Bjergaard J, Philip P, Larsen SO, et al.: Therapy-related myelodysplasia and acute myeloid leukemia: cytogenetic characteristics of 115 consecutive cases and risk in seven cohorts of patients treated intensively for malignant diseases in the Copenhagen series. Leukemia 1993, 7:1975–1986.PubMedGoogle Scholar
  41. 41.
    Amann JM, Nip J, Strom DK, et al.: ETO, a target of t(8,21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain. Mol Cell Biol 2001, 21:6470–6483.PubMedCrossRefGoogle Scholar
  42. 42.
    Moe-Behrens GH, Pandolfi PP: Targeting aberrant transcriptional repression in acute myeloid leukemia. Rev Clin Exp Hematol 2003, 7:139–159.PubMedGoogle Scholar
  43. 43.
    Wang J, Hoshino T, Redner RL, et al.: ETO, fusion partner in t(8,21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex. Proc Natl Acad Sci U S A 1998, 95:10860–10865.PubMedCrossRefGoogle Scholar
  44. 44.
    Lenz G, Dreyling M, Schiegnitz E, et al.: Moderate increase of secondary hematologic malignancies after myeloablative radiochemotherapy and autologous stem-cell transplantation in patients with indolent lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group. J Clin Oncol 2004, 22:4926–4933.PubMedCrossRefGoogle Scholar
  45. 45.
    Milligan DW, Kochethu G, Dearden C, et al.: High incidence of myelodysplasia and secondary leukaemia in the UK Medical Research Council Pilot of autografting in chronic lymphocytic leukaemia. Br J Haematol 2006, 133:173–175.PubMedCrossRefGoogle Scholar
  46. 46.
    Linassier C, Barin C, Calais G, et al.: Early secondary acute myelogenous leukemia in breast cancer patients after treatment with mitoxantrone, cyclophosphamide, fluorouracil and radiation therapy. Ann Oncol 2000, 11:1289–1294.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Department of LeukemiaThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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