TY - JOUR
T1 - Cancer and myeloid clonal evolution in the short telomere syndromes
AU - Schratz, Kristen E.
AU - Armanios, Mary
N1 - Funding Information:
Work in the Armanios group is supported by the United States National Institutes of Health grants CA225027 and HL119476, and support from the S&R, Gary Williams, and Commonwealth Foundations (to M.A.). We acknowledge a gift in the name of Mrs. P. Godrej (M.A.). KES is supported by NIH T32 HL007525 and the Turock Scholars Fund at the Telomere Center at Johns Hopkins.
Funding Information:
Work in the Armanios group is supported by the United States National Institutes of Health grants CA225027 and HL119476 , and support from the S&R, Gary Williams, and Commonwealth Foundations (to M.A.). We acknowledge a gift in the name of Mrs. P. Godrej (M.A.). KES is supported by NIH T32 HL007525 and the Turock Scholars Fund at the Telomere Center at Johns Hopkins.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/2
Y1 - 2020/2
N2 - The short telomere syndromes are considered the most common premature aging disorders. Although studies in genetically modified cells and animal models have suggested telomere dysfunction may promote genome instability, only a minority of humans with inherited loss-of-function mutations in telomerase and related genes develop cancer. Solid tumors are overall rare, and the vast majority of cancers are bone marrow-derived with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) comprising three-quarter of cases. In contrast to young short telomere syndrome patients who develop aplastic anemia, MDS and AML are usually diagnosed in adults who have milder short telomere defects. Here, we dissect the mechanisms by which these two bone marrow failure states, aplastic anemia and MDS-AML, evolve in the setting of varying degrees of telomere shortening. We discuss of these observations for patient care as well as for understanding the genetics and biology of age-related myeloid clonal evolution.
AB - The short telomere syndromes are considered the most common premature aging disorders. Although studies in genetically modified cells and animal models have suggested telomere dysfunction may promote genome instability, only a minority of humans with inherited loss-of-function mutations in telomerase and related genes develop cancer. Solid tumors are overall rare, and the vast majority of cancers are bone marrow-derived with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) comprising three-quarter of cases. In contrast to young short telomere syndrome patients who develop aplastic anemia, MDS and AML are usually diagnosed in adults who have milder short telomere defects. Here, we dissect the mechanisms by which these two bone marrow failure states, aplastic anemia and MDS-AML, evolve in the setting of varying degrees of telomere shortening. We discuss of these observations for patient care as well as for understanding the genetics and biology of age-related myeloid clonal evolution.
UR - http://www.scopus.com/inward/record.url?scp=85082794211&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082794211&partnerID=8YFLogxK
U2 - 10.1016/j.gde.2020.02.019
DO - 10.1016/j.gde.2020.02.019
M3 - Review article
C2 - 32276199
AN - SCOPUS:85082794211
SN - 0959-437X
VL - 60
SP - 112
EP - 118
JO - Current Opinion in Genetics and Development
JF - Current Opinion in Genetics and Development
ER -