TY - JOUR
T1 - Myelodysplastic syndrome
T2 - An inability to appropriately respond to damaged DNA?
AU - Zhou, Ting
AU - Hasty, Paul
AU - Walter, Christi A.
AU - Bishop, Alexander J.R.
AU - Scott, Linda M.
AU - Rebel, Vivienne I.
N1 - Funding Information:
This work was supported by the National Institute of Aging (grant 5R21AG033339 to V.I.R. and C.A.W.), the National Institute of Environmental Health Sciences (grant 1RO1ES022054 to P.E.H. and V.I.R.), and Hyundai Hope on Wheels (to A.J.R.B. and V.I.R.).
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.exphem.2013.04.008
DO - 10.1016/j.exphem.2013.04.008
M3 - Review article
C2 - 23643835
AN - SCOPUS:84880755300
VL - 41
SP - 665
EP - 674
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 8
ER -