TY - JOUR
T1 - Mechanisms of somatic transformation in inherited bone marrow failure syndromes
AU - Choijilsuren, Haruna Batzorig
AU - Park, Yeji
AU - Jung, Moonjung
N1 - Funding Information:
This work was supported in part by National Heart Lung and Blood Institute grant K99 HL150628 (M.J.). Authors thank Dr. Robert Brodsky and Dr. Amy DeZern for their constructive feedback.
Publisher Copyright:
© 2021 by The American Society of Hematology
PY - 2021/12/10
Y1 - 2021/12/10
N2 - Inherited bone marrow failure syndromes (IBMFS) cause hematopoietic stem progenitor cell (HSPC) failure due to germline mutations. Germline mutations influence the number and fitness of HSPC by various mechanisms, for example, abnormal ribosome biogenesis in Shwachman-Diamond syndrome and Diamond-Blackfan anemia, unresolved DNA cross-links in Fanconi anemia, neutrophil maturation arrest in severe congenital neutropenia, and telomere shortening in short telomere syndrome. To compensate for HSPC attrition, HSPCs are under increased replication stress to meet the need for mature blood cells. Somatic alterations that provide full or partial recovery of functional deficit implicated in IBMFS can confer a growth advantage. This review discusses results of recent genomic studies and illustrates our new understanding of mechanisms of clonal evolution in IBMFS.
AB - Inherited bone marrow failure syndromes (IBMFS) cause hematopoietic stem progenitor cell (HSPC) failure due to germline mutations. Germline mutations influence the number and fitness of HSPC by various mechanisms, for example, abnormal ribosome biogenesis in Shwachman-Diamond syndrome and Diamond-Blackfan anemia, unresolved DNA cross-links in Fanconi anemia, neutrophil maturation arrest in severe congenital neutropenia, and telomere shortening in short telomere syndrome. To compensate for HSPC attrition, HSPCs are under increased replication stress to meet the need for mature blood cells. Somatic alterations that provide full or partial recovery of functional deficit implicated in IBMFS can confer a growth advantage. This review discusses results of recent genomic studies and illustrates our new understanding of mechanisms of clonal evolution in IBMFS.
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U2 - 10.1182/hematology.2021000271
DO - 10.1182/hematology.2021000271
M3 - Article
C2 - 34889377
AN - SCOPUS:85122428689
SN - 1520-4391
VL - 2021
SP - 390
EP - 398
JO - Hematology (United States)
JF - Hematology (United States)
IS - 1
ER -