Adaptive and Maladaptive Clonal Hematopoiesis in Telomere Biology Disorders.

Terra Lasho, Mrinal M Patnaik

Current hematologic malignancy reports 2024 Feb

filter terms:

Telomere biology disorders (TBDs) are germline-inherited conditions characterized by reduction in telomerase function, accelerated shortening of telomeres, predisposition to organ-failure syndromes, and increased risk of neoplasms, especially myeloid malignancies. In normal cells, critically short telomeres trigger apoptosis and/or cellular senescence. However, the evolutionary mechanism by which TBD-related telomerase-deficient cells can overcome this fitness constraint remains elusive. Preliminary data suggests the existence of adaptive somatic mosaic states characterized by variants in TBD-related genes and maladaptive somatic mosaic states that attempt to overcome hematopoietic fitness constraints by alternative methods leading to clonal hematopoiesis. TBDs are both rare and highly heterogeneous in presentation, and the association of TBD with malignant transformation is unclear. Understanding the clonal complexity and mechanisms behind TBD-associated molecular signatures that lead to somatic adaptation in the setting of defective hematopoiesis will help inform therapy and treatment for this set of diseases. © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Terra Lasho, Mrinal M Patnaik. Adaptive and Maladaptive Clonal Hematopoiesis in Telomere Biology Disorders. Current hematologic malignancy reports. 2024 Feb;19(1):35-44