Dissecting clonal hematopoiesis in the myeloid compartment of chronic lymphocytic leukemia and Richter transformation - PubMed
5 days ago
- #Richter transformation
- #chronic lymphocytic leukemia
- #clonal hematopoiesis
- Clonal hematopoiesis (CH) was studied in the myeloid compartment of 488 newly diagnosed chronic lymphocytic leukemia (CLL) patients using a 28-gene panel on granulocyte genomic DNA (gDNA).
- CH was found in 47.3% of patients (231 cases) and was restricted to the myelomonocytic compartment, not present in CLL cells, as confirmed by single-cell DNA sequencing.
- CH was associated with shorter overall survival (OS) (HR 1.36, P = 0.023), with TET2 mutations independently predicting inferior OS (HR 1.62, P = 0.01).
- CH correlated with higher incidence of Grade ≥ 3 neutropenia after venetoclax-based regimens (P = 0.004).
- Bruton tyrosine kinase (BTK) and BCL2 inhibitors did not induce CH expansion, but chemotherapy did.
- CH was significantly associated with a higher risk of second hematological malignancies in chemo-exposed patients.
- Single-cell RNA sequencing revealed that CH+ CLL patients had a less exhausted T-cell phenotype and a higher pro-inflammatory profile.
- CH ASXL1 mutations independently increased Richter transformation (RT) risk (HR 11.19, P < 0.001).
- CH impacts survival, therapy toxicity, transformation risk, and T-cell immune compartment in CLL.