Vulnerability of SRSF2-mutated chronic myelomonocytic leukemia to perturbation of the cGAS-STING pathway.

ABSTRACT:

Abstract

Chronic myelomonocytic leukemia (CMML) is characterized by monocytosis in blood and bone marrow and natural progression to acute myeloid leukemia (AML) in ≤30% of patients. The mutation landscape of CMML has been reported, and animal models that recapitulate its clinicopathologic features and progression are needed. We report a CMML zebrafish model based on transgenic SRSF2P95H expression that closely resembled the human disease. Hematological assessment of the transgenic animals showed myelodysplasia, monocytosis, and leukemia transformation. Transcriptomic analysis confirmed global splicing alterations and identified inflammatory phenotypes associated with activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. DNA damage, R-loop fo

SUBMITTER: Chen Y 

PROVIDER: S-EPMC12874312 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature