Format

Send to

Choose Destination
Int J Hematol. 2015 Nov;102(5):513-22. doi: 10.1007/s12185-015-1870-5. Epub 2015 Oct 6.

Aging, clonal hematopoiesis and preleukemia: not just bad luck?

Author information

1
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network (UHN), 610 University Ave, Toronto, ON, M5G 2M9, Canada. liranshlush3@gmail.com.
2
Weizmann Institute of Science, Rehovot, Israel. liranshlush3@gmail.com.
3
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network (UHN), 610 University Ave, Toronto, ON, M5G 2M9, Canada.
4
Weizmann Institute of Science, Rehovot, Israel.

Abstract

Chronological human aging is associated with a number of changes in the hematopoietic system, occurring at many levels from stem to mature cells, and the marrow microenvironment as well. This review will focus mainly on the aging of hematopoietic stem and progenitor cells (HSPCs), and on the associated increases in the incidence of hematological malignancies. HSPCs manifest reduced function and acquire molecular changes with chronological aging. Furthermore, while for many years it has been known that the human hematopoietic system becomes increasingly clonal with chronological aging (clonal hematopoiesis), only in the last few years has it become clear that clonal hematopoiesis may result from the accumulation of preleukemic mutations in HSPCs. Such mutations confer a selective advantage that leads to clonal hematopoiesis, and that may occasionally result in the development of leukemia, and define the existence of both preleukemic stem cells, and of 'preleukemia' as a clinical entity. While it is well appreciated that clonal hematopoiesis is very common in the elderly, several questions remain unanswered: why and how does clonal hematopoiesis develop? How is clonal hematopoiesis related to the age-related changes observed in the hematopoietic system? And why do only some individuals with clonal hematopoiesis develop leukemia?

KEYWORDS:

Aging; Clonal hematopoeisis; Preleukemia

PMID:
26440972
DOI:
10.1007/s12185-015-1870-5
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center