title: Myelodysplastic syndrome: an inability to appropriately respond to damaged DNA?
abstract: Myelodysplastic syndrome (MDS) is considered a hematopoietic stem cell disease that is characterized by abnormal hematopoietic differentiation and a high propensity to develop acute myeloid leukemia. It is mostly associated with advanced age, but also with prior cancer therapy and inherited syndromes related to abnormalities in DNA repair. Recent technologic advances have led to the identification of a myriad of frequently occurring genomic perturbations associated with MDS. These observations suggest that MDS and its progression to acute myeloid leukemia is a genomic instability disorder, resulting from a stepwise accumulation of genetic abnormalities. The notion is now emerging that the underlying mechanism of this disease could be a defect in one or more pathways that are involved in responding to or repairing damaged DNA. In this review, we discuss these pathways in relationship to a large number of studies performed with MDS patient samples and MDS mouse models. Moreover, in view of our current understanding of how DNA damage response and repair pathways are affected by age in hematopoietic stem cells, we also explore how this might relate to MDS development.
authors: Greehey Children's Cancer Research Center, University of Texas Health Science Center at San Antonio, TX 78229, USA.
authors: Ting
authors: T
authors: Zhou
authors: Paul
authors: P
authors: Hasty
authors: Christi A
authors: CA
authors: Walter
authors: Alexander J R
authors: AJ
authors: Bishop
authors: Linda M
authors: LM
authors: Scott
authors: Vivienne I
authors: VI
authors: Rebel
mesh_terms: D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D004260:DNA Repair; D018450:Disease Progression; D042822:Genomic Instability; D006410:Hematopoiesis; D006801:Humans; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology
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