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SF3B1 Mutations Frequently Occur With Both ATM Mutations and TP53 Mutations In CLL Patients

Navrkalova V,Malcikova J,Kantorova B et al.

Key Points:

Assess association between SF3B1 mutations and most adverse classic genetic lesions represented by TP53 mutations and del(11q).
Investigate association between SF3B1 mutations and ATM mutations.
Delineate SF3B1 mutation profile and proportion.
338 patients characterized by prevalence of unmutated IGHV (72%).
82.5% of patients previously untreated.
SF3B1 mutation in 17.5% (59/338), TP53 mutation in 20% (68/338), and del(11q) in 27.5% (93/338) of cases.
Genetic defects more frequent in treated patients (SF3B1: P=0.008, TP53: P<0.0001, del(11q): P=0.0295).
Frequent co-occurrence of SF3B1 and TP53 mutations.
28% (19/68) of p53-affected patients in comparison with 15% (40/270) of p53-wt patients harbored SF3B1 mutation (P=0.019).
SF3B1 mutation frequency in patients with del(11q) also apparent but not significant.
37 patients SF3B1 and ATM mutations frequently co-occur: 8/21 ATM-mutated patients (38%) but only 2/16 ATM-TP53-wt patients (12.5%) exhibited SF3B1 mutation (P=0.137).

Implications:

SF3B1 mutations frequently overlap with mutations in DNA damage response pathway genes, especially in prognostically unfavorable cohort.