<i>NOTCH1</i> and <i>SF3B1</i> mutations in chronic lymphocytic leukemia with their clinical associations

Chronic lymphocytic leukemia (CLL) exhibits heterogeneous clinical outcomes influenced by chromosomal aberrations and genetic mutations. <i>NOTCH1</i> and <i>SF3B1</i> 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 <i>NOTCH1</i> exon 34 and <i>SF3B1</i> exons 15-16. <i>In silico</i> pathogenicity was predicted using I-Mutant and PolyPhen-2. Mutations were found in 23.3% of patients (14/60), including the recurrent <i>NOTCH1</i> c.7541_7542delCT (p.P2514Rfs) (10%) and <i>SF3B1</i> c.2098A > G (p.K700E) (6.6%). Two novel <i>NOTCH1</i> 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 <i>NOTCH1</i> and <i>SF3B1</i> mutations associated with adverse features, expanding the CLL mutational spectrum and offering valuable prognostic and therapeutic insights.