TY - JOUR
T1 - Stem and progenitor cell alterations in myelodysplastic syndromes
AU - Shastri, Aditi
AU - Will, Britta
AU - Steidl, Ulrich
AU - Verma, Amit
N1 - Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/3/23
Y1 - 2017/3/23
N2 - Recent studies have demonstrated that myelodysplastic syndromes (MDSs) arise from a small population of diseaseinitiating hematopoietic stem cells (HSCs) that persist and expand through conventional therapies and are major contributors to disease progression and relapse. MDS stem and progenitor cells are characterized by key founder and driver mutations and are enriched for cytogenetic alterations. Quantitative alterations in hematopoietic stem and progenitor cell (HSPC) numbers are also seen in a stagespecific manner in human MDS samples as well as in murine models of the disease. Overexpression of several markers such as interleukin-1 (IL-1) receptor accessory protein (IL1RAP), CD99, T-cell immunoglobulin mucin-3, and CD123 have begun to differentiate MDS HSPCs from healthy counterparts. Overactivation of innate immune components such as Toll-like receptors, IL-1 receptor-associated kinase/ tumor necrosis factor receptor-associated factor-6, IL8/CXCR2, and IL1RAP signaling pathways has been demonstrated in MDS HSPCsandisbeing targeted therapeutically in preclinical and early clinical studies. Other dysregulated pathways such as signal transducer and activator of transcription 3, tyrosine kinase with immunoglobulinlike and EGF-like domains 1/angiopoietin-1, p21-activated kinase, microRNA 21, and transforming growth factor b are also being explored as therapeutic targets against MDS HSPCs. Taken together, these studies have demonstrated that MDS stem cells are functionally critical for the initiation, transformation, and relapse of disease and need to be targeted therapeutically for future curative strategies in MDSs.
AB - Recent studies have demonstrated that myelodysplastic syndromes (MDSs) arise from a small population of diseaseinitiating hematopoietic stem cells (HSCs) that persist and expand through conventional therapies and are major contributors to disease progression and relapse. MDS stem and progenitor cells are characterized by key founder and driver mutations and are enriched for cytogenetic alterations. Quantitative alterations in hematopoietic stem and progenitor cell (HSPC) numbers are also seen in a stagespecific manner in human MDS samples as well as in murine models of the disease. Overexpression of several markers such as interleukin-1 (IL-1) receptor accessory protein (IL1RAP), CD99, T-cell immunoglobulin mucin-3, and CD123 have begun to differentiate MDS HSPCs from healthy counterparts. Overactivation of innate immune components such as Toll-like receptors, IL-1 receptor-associated kinase/ tumor necrosis factor receptor-associated factor-6, IL8/CXCR2, and IL1RAP signaling pathways has been demonstrated in MDS HSPCsandisbeing targeted therapeutically in preclinical and early clinical studies. Other dysregulated pathways such as signal transducer and activator of transcription 3, tyrosine kinase with immunoglobulinlike and EGF-like domains 1/angiopoietin-1, p21-activated kinase, microRNA 21, and transforming growth factor b are also being explored as therapeutic targets against MDS HSPCs. Taken together, these studies have demonstrated that MDS stem cells are functionally critical for the initiation, transformation, and relapse of disease and need to be targeted therapeutically for future curative strategies in MDSs.
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U2 - 10.1182/blood-2016-10-696062
DO - 10.1182/blood-2016-10-696062
M3 - Review article
C2 - 28159737
AN - SCOPUS:85016256866
SN - 0006-4971
VL - 129
SP - 1586
EP - 1594
JO - Blood
JF - Blood
IS - 12
ER -