PUMA-induced apoptosis drives bone marrow failure and genomic instability in telomerase-deficient mice.

ABSTRACT: Bone marrow failure is a severe complication of human telomere biology disorders and predisposes individuals to secondary leukemia. A deeper understanding of this process could offer significant clinical benefits. Using a preclinical mouse model deficient in the RNA component of the telomerase (mTerc), we demonstrate that bone marrow failure results from excessive apoptosis, predominantly mediated by the pro-apoptotic p53 target PUMA. Genetic ablation of Puma alleviates hematological phenotypes and reduces the risk of lethal bone marrow failure while preserving genomic stability. Mechanistically, PUMA deficiency decreases the sensitivity of hematopoietic cells to lethal stressors, including critically short telomeres. As a consequence, reduced compensatory turnover of hematopoietic progeni

SUBMITTER: Molnar C 

PROVIDER: S-EPMC12811261 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature