title: Therapy-related myeloid neoplasms: does knowing the origin help to guide treatment?
abstract: Therapy-related myeloid neoplasms (t-MN) combine t-MDS and therapy related acute myeloid leukemia (t-AML) patients in one entity because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. In contrast, treatment with alkylating agents has been associated with a longer latency, an initial MDS phase, adverse cytogenetics, and a poor prognosis. The pathogenesis of t-MN can be explained by direct induction of an oncogene through chromosomal translocations, induction of genetic instability, or selection of a preexisting treatment-resistant hematopoietic stem cell clone. Recent evidence has highlighted the importance of the last mechanism and explains the high frequency of TP53 mutations in patients with t-MN. After previous cytotoxic therapy, patients present with specific vulnerabilities, especially evident from the high nonrelapse mortality in patients with t-MN after allogeneic hematopoietic cell transplantation. Here, the prognostic impact of currently known risk factors and the therapeutic options in different patient subgroups will be discussed.
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D014178:Translocation, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; C497422:KMT2A protein, human; C529663:MLL-MLLT3 fusion protein, human; D015514:Oncogene Proteins, Fusion; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase