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Sill, H; Olipitz, W; Zebisch, A; Schulz, E; Wölfler, A.
Therapy-related myeloid neoplasms: pathobiology and clinical characteristics.
Br J Pharmacol. 2011; 162(4): 792-805. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Schulz Eduard
Sill Heinz
Wölfler Albert
Zebisch Armin
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Abstract:
Therapy-related myeloid neoplasms (t-MNs) are serious long-term consequences of cytotoxic treatments for an antecedent disorder. t-MNs are observed after ionizing radiation as well as conventional chemotherapy including alkylating agents, topoisomerase-II-inhibitors and antimetabolites. In addition, adjuvant use of recombinant human granulocyte-colony stimulating factor may also increase the risk of t-MNs. There is clinical and biological overlap between t-MNs and high-risk de novo myelodysplastic syndromes and acute myeloid leukaemia suggesting similar mechanisms of leukaemogenesis. Human studies and animal models point to a prominent role of genetic susceptibilty in the pathogenesis of t-MNs. Common genetic variants have been identified that modulate t-MN risk, and t-MNs have been observed in some cancer predisposition syndromes. In either case, establishing a leukaemic phenotype requires acquisition of somatic mutations - most likely induced by the cytotoxic treatment. Knowledge of the specific nature of the initiating exposure has allowed the identification of crucial pathogenetic mechanisms and for these to be modelled in vitro and in vivo. Prognosis of patients with t-MNs is dismal and at present, the only curative approach for the majority of these individuals is haematopoietic stem cell transplantation, which is characterized by high transplant-related mortality rates. Novel transplantation strategies using reduced intensity conditioning regimens as well as novel drugs - demethylating agents and targeted therapies - await clinical testing and may improve outcome. Ultimately, individual assessment of genetic risk factors may translate into tailored therapies and establish a strategy for reducing t-MN incidences without jeopardizing therapeutic success rates for the primary disorders.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Antineoplastic Agents - adverse effects
Genetic Predisposition to Disease -
Hematopoietic Stem Cell Transplantation -
Humans -
Leukemia, Myeloid, Acute - chemically induced Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - physiopathology Leukemia, Myeloid, Acute - therapy
Myelodysplastic Syndromes - chemically induced Myelodysplastic Syndromes - genetics Myelodysplastic Syndromes - physiopathology Myelodysplastic Syndromes - therapy
Neoplasms, Second Primary - chemically induced Neoplasms, Second Primary - genetics Neoplasms, Second Primary - physiopathology Neoplasms, Second Primary - therapy
Prognosis -
Radiotherapy - adverse effects

Find related publications in this database (Keywords)
therapy-related myeloid neoplasms
therapy-related myelodysplastic syndrome
therapy-related acute myeloid leukaemia
ionizing radiation
alkylating agents
topoisomerase-II-inhibitors
antimetabolites
granulocyte-colony stimulating factor
genetic susceptibility
stem cell transplantation
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