Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease

Camilla Bertuzzo Veiga; Erin M Lawrence; Andrew J Murphy; Marco J Herold; Dragana Dragoljevic

doi:10.3390/cancers13081968

Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease

Cancers (Basel). 2021 Apr 19;13(8):1968. doi: 10.3390/cancers13081968.

Authors

Camilla Bertuzzo Veiga^{1

2}, Erin M Lawrence^{3

4}, Andrew J Murphy^{1

5

6}, Marco J Herold^{3

4}, Dragana Dragoljevic^{1

5

6}

Affiliations

¹ Division of Immunometabolism, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
² Department of Anatomy and Physiology, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
³ Walter and Eliza Hall Institute of Medical Research, 1 G Royal Parade, Parkville, Melbourne, VIC 3052, Australia.
⁴ Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3052, Australia.
⁵ Department of Diabetes, Department of Immunology, Monash University, Clayton, VIC 3004, Australia.
⁶ Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC 3052, Australia.

Abstract

The development of myelodysplasia syndromes (MDS) is multiphasic and can be driven by a plethora of genetic mutations and/or abnormalities. MDS is characterized by a hematopoietic differentiation block, evidenced by increased immature hematopoietic cells, termed blast cells and decreased mature circulating leukocytes in at least one lineage (i.e., cytopenia). Clonal hematopoiesis of indeterminate potential (CHIP) is a recently described phenomenon preceding MDS development that is driven by somatic mutations in hemopoietic stem cells (HSCs). These mutant HSCs have a competitive advantage over healthy cells, resulting in an expansion of these clonal mutated leukocytes. In this review, we discuss the multiphasic development of MDS, the common mutations found in both MDS and CHIP, how a loss-of-function in these CHIP-related genes can alter HSC function and leukocyte development and the potential disease outcomes that can occur with dysfunctional HSCs. In particular, we discuss the novel connections between MDS development and cardiovascular disease.

Keywords: ASXL1; DNMT3A; JAK2; P53; TET2; cardiovascular disease; clonal hematopoiesis and indeterminate potential (CHIP); hematopoietic stem cell (HSC); myelodysplasia syndrome.

Publication types

Review