Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Clonal Hematopoiesis and Myeloid Neoplasms in the Context of Telomere Biology Disorders

Clonal Hematopoiesis and Myeloid Neoplasms in the Context of Telomere Biology Disorders Purpose of ReviewTelomere biology disorders (TBDs) are cancer-predisposing multisystemic diseases that portend a higher risk of transforming into myeloid neoplasms (MNs). Due to the rarity and high variability of clinical presentations, TBD-specific characteristics of MN and the mechanisms behind this predisposition are not well defined. Herein, we review recent studies on TBD patient cohorts describing myeloid transformation events and summarize efforts to develop screening and treatment guidelines for these patients.Recent FindingsPreliminary studies have indicated that TBD patients have a higher prevalence of somatic genetic alterations in hematopoietic cells, an age-related phenomenon, also known as clonal hematopoiesis; increasing predisposition to MN. The CH mutational landscape in TBD differs from that observed in non-TBD patients and preliminary data suggest a higher frequency of somatic mutations in the DNA repair mechanism pathway. Although initial studies did not observe specific features of MN in TBD patients, certain events are common in TBD, such as hypocellular bone marrows. The mechanisms of MN development need further elucidation.SummaryCurrent management options for MN-TBD patients need to be individualized and tailored as per the clinical context. Because of the high sensitivity to alkylator chemotherapy and radiation conferred by short telomeres, non-cytotoxic targeted therapies and immunotherapy are ideal therapeutic options, but these therapies are still being tested in clinical trials. Defining the mechanisms of CH evolution in TBD and identifying risk factors leading to MN evolution will allow for the development of screening and treatment guidelines for these patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Hematologic Malignancy Reports Springer Journals

Clonal Hematopoiesis and Myeloid Neoplasms in the Context of Telomere Biology Disorders

Download PDF
8 pages

Loading next page...
 
/lp/springer-journals/clonal-hematopoiesis-and-myeloid-neoplasms-in-the-context-of-telomere-r0mE4hJxco

References (45)

Publisher
Springer Journals
Copyright
Copyright © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022
ISSN
1558-8211
eISSN
1558-822X
DOI
10.1007/s11899-022-00662-8
Publisher site
See Article on Publisher Site

Abstract

Purpose of ReviewTelomere biology disorders (TBDs) are cancer-predisposing multisystemic diseases that portend a higher risk of transforming into myeloid neoplasms (MNs). Due to the rarity and high variability of clinical presentations, TBD-specific characteristics of MN and the mechanisms behind this predisposition are not well defined. Herein, we review recent studies on TBD patient cohorts describing myeloid transformation events and summarize efforts to develop screening and treatment guidelines for these patients.Recent FindingsPreliminary studies have indicated that TBD patients have a higher prevalence of somatic genetic alterations in hematopoietic cells, an age-related phenomenon, also known as clonal hematopoiesis; increasing predisposition to MN. The CH mutational landscape in TBD differs from that observed in non-TBD patients and preliminary data suggest a higher frequency of somatic mutations in the DNA repair mechanism pathway. Although initial studies did not observe specific features of MN in TBD patients, certain events are common in TBD, such as hypocellular bone marrows. The mechanisms of MN development need further elucidation.SummaryCurrent management options for MN-TBD patients need to be individualized and tailored as per the clinical context. Because of the high sensitivity to alkylator chemotherapy and radiation conferred by short telomeres, non-cytotoxic targeted therapies and immunotherapy are ideal therapeutic options, but these therapies are still being tested in clinical trials. Defining the mechanisms of CH evolution in TBD and identifying risk factors leading to MN evolution will allow for the development of screening and treatment guidelines for these patients.

Journal

Current Hematologic Malignancy Reports – Springer Journals

Published: Jun 1, 2022

Keywords: Telomere biology disorders; Clonal hematopoiesis; Myeloid neoplasm

There are no references for this article.