NOTCH1 and SF3B1 mutations in chronic lymphocytic leukemia with their clinical associations

Chronic lymphocytic leukemia (CLL) exhibits heterogeneous clinical outcomes influenced by chromosomal aberrations and genetic mutations. NOTCH1 and SF3B1 mutations are critical prognostic markers linked to disease progression and therapy resistance. This study analyzed 60 CLL patients from Hiwa Hospital (Sulaymaniyah, Iraq). Hematological parameters were assessed, and genomic DNA was sequenced for NOTCH1 exon 34 and SF3B1 exons 15-16. In silico pathogenicity was predicted using I-Mutant and PolyPhen-2. Mutations were found in 23.3% of patients (14/60), including the recurrent NOTCH1 c.7541_7542delCT (p.P2514Rfs) (10%) and SF3B1 c.2098A > G (p.K700E) (6.6%). Two novel NOTCH1 variants (PX317668 and PX317669) were also identified. Mutated cases showed advanced Binet stages, elevated LDH, and reduced hemoglobin (HGB) and platelet (PLT) counts. These findings reveal a notable prevalence of NOTCH1 and SF3B1 mutations associated with adverse features, expanding the CLL mutational spectrum and offering valuable prognostic and therapeutic insights.