Prognostic relevance of RUNX1 mutations in T-cell acute lymphoblastic leukemia

Abstract

The runt-related transcription factor 1, RUNX1, is crucial in the development of myeloid and lymphoid cell lineages and has been reported to be mutated in myeloid malignancies in approximately 30% of cases. In this study, the mutational status of RUNX1 was investigated in 128 acute lymphoblastic leukemia patients. We detected a mutation rate of 18.3% (13 of 71) in patients with T-cell acute lymphoblastic leukemia, 3.8% (2 of 52) in patients with B-cell acute lymphoblastic leukemia and no mutation (0 of 5) in patients with natural killer cell leukemia, respectively. In T-cell acute lymphoblastic leukemia patients, RUNX1 mutations were significantly associated with higher age (P=0.017) and lower white blood cell count (P=0.038). Moreover, an inferior outcome was observed in the subgroup of early T-cell acute lymphoblastic leukemia patients carrying RUNX1 mutations for overall survival (P=0.043). In conclusion, RUNX1 mutations are an important novel biomarker for a comprehensive characterization of T-cell acute lymphoblastic leukemia with poor prognostic impact and have implications for use also in monitoring disease.

Figure 1.

(A) Distribution of RUNX1 mutations between the three subgroups of T-ALL. (B) Distribution of RUNX1 mutations in ALL. Location of the 17 mutations in RUNX1 according to the functional domains as detected in 15 patients. Vertical arrows indicate the location of the mutations; corresponding concurrent mutation pairs of the same patient are connected by horizontal lines. Two mutations marked with an asterisk indicate the 2 B-ALL cases. (C) Kaplan–Meier overall survival estimates including 30 early T-ALL cases. Data are shown for overall survival of T-ALL patients separated into two groups of RUNX1-mutated (n=8) and RUNX1 wild-type patients (n=22; alive at two years 28.6% vs. 46.0%).