Cell senescence and malignant transformation in the inherited bone marrow failure syndromes: Overlapping pathophysiology with therapeutic implications.

Authors

Emma M Groarke, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Electronic address: Emma.Groarke@nih.gov
Rodrigo T Calado, Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
Johnson M Liu, Division of Hematology, Maine Medical Center, Portland, ME

Document Type

Article

Publication Date

1-1-2022

Institution/Department

Hematology

Journal Title

Seminars in hematology

MeSH Headings

Anemia, Aplastic, Bone Marrow Diseases, Cellular Senescence, Congenital Bone Marrow Failure Syndromes, Fanconi Anemia, Humans

Abstract

Fanconi anemia, telomeropathies and ribosomopathies are members of the inherited bone marrow failure syndromes, rare genetic disorders that lead to failure of hematopoiesis, developmental abnormalities, and cancer predisposition. While each disorder is caused by different genetic defects in seemingly disparate processes of DNA repair, telomere maintenance, or ribosome biogenesis, they appear to lead to a common pathway characterized by premature senescence of hematopoietic stem cells. Here we review the experimental data on senescence and inflammation underlying marrow failure and malignant transformation. We conclude with a critical assessment of current and future therapies targeting these pathways in inherited bone marrow failure syndromes patients.

ISSN

1532-8686

First Page

30

Last Page

37

Recommended Citation

Groarke EM, Calado RT, Liu JM. Cell senescence and malignant transformation in the inherited bone marrow failure syndromes: Overlapping pathophysiology with therapeutic implications. Semin Hematol. 2022;59(1):30-37. doi:10.1053/j.seminhematol.2022.01.003