Clonal Hematopoiesis and Myeloid Neoplasms in the Context of Telomere Biology Disorders.
Alejandro FerrerAbhishek A MangaonkarMrinal M PatnaikPublished in: Current hematologic malignancy reports (2022)
Preliminary 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. Current 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.
Keyphrases
- end stage renal disease
- newly diagnosed
- ejection fraction
- chronic kidney disease
- risk factors
- clinical trial
- dna repair
- peritoneal dialysis
- prognostic factors
- gene expression
- acute myeloid leukemia
- cell death
- squamous cell carcinoma
- dna damage
- immune response
- bone marrow
- patient reported outcomes
- electronic health record
- dna methylation
- deep learning
- signaling pathway
- study protocol
- phase ii
- bone loss