Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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.
Doi: 10.1111/j.1476-5381.2010.01100.x
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- Führende Autor*innen der Med Uni Graz
- Sill Heinz
- Co-Autor*innen der Med Uni Graz
- Schulz Eduard
- 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