Comprehensive analysis of clinical, pathological, and molecular features in chronic myelomonocytic leukemia: frequent ASXL1 and NRAS mutations and higher mutation burden in myeloproliferative CMML compared to myelodysplastic CMML

Abstract

Various aspects of myeloproliferative chronic myelomonocytic leukemia (MP-CMML) and myelodysplastic CMML (MD-CMML) have been reported but inconsistencies remain. This study conducted a comprehensive retrospective analysis of clinical, pathological, and molecular data from a cohort of CMML. The results revealed a higher frequency of ASXL1 and NRAS mutations and a greater mutation burden in MP-CMML, characterized by more tier 1 or 2 variants and dominant mutations. Significant genotype-phenotype correlations were observed, including distinct patterns within MD-CMML subgroups. Additionally, NRAS or RUNX1 mutations and an abnormal karyotype were associated with worse overall survival or progression-free survival. These findings underscore the distinct molecular and pathological differences between MP-CMML and MD-CMML, highlighting the more aggressive nature of MP-CMML and the need for tailored treatment strategies.