title: Pharmacological differentiation and anti-apoptotic therapy in myelodysplastic syndromes.
abstract: The haematological diversity of myelodysplastic syndromes (MDS) mandates that therapeutic strategies for this disease be guided by an understanding of the disease biology. Insights into the pathobiology of this disease have given rise to novel treatment strategies which exploit basic biological disturbances. Myelodysplastic bone marrow progenitors from patients with low leukaemia burden display an accelerated senescence phenotype which is characterised by impaired response to trophic signals and premature apoptotic death of primitive haematopoietic progenitors. Elaboration of aptogenic cytokines such as TNF-alpha and IL-1beta may reinforce this sequence by up-regulating cellular expression of fas ligand and its cognate receptor, suppressing responsiveness to growth factor stimulation, and accelerating apoptotic cell death. Inactivation of p15 or other tumour suppressor genes antedate disease progression and the emergence of blast populations with reduced capacity for fas mediated cell death. Herein we review the current understanding of the pathobiology of MDS and promising strategies for therapeutic intervention.
authors: Section of Hematology/Oncology and the Bone Marrow Transplant Program, The Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724-5024, USA.
authors: A F
authors: AF
authors: List
mesh_terms: D004999:Amifostine / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis; D001374:Azacitidine / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000503:physiopathology*; D010654:Phenylbutyrates / Q000627:therapeutic use; D011355:Prodrugs / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D010654:Phenylbutyrates; D011355:Prodrugs; D004999:Amifostine; D001374:Azacitidine