Comparison of mutational profiles and clinical outcomes in patients with acute myeloid leukemia with mutated RUNX1 versus acute myeloid leukemia with myelodysplasia-related changes with mutated RUNX1

Abstract

Studies comparing the prognostic role of RUNX1 mutations (RUNX1^mut) in acute myeloid leukemia (AML) and acute myeloid leukemia-with myelodysplasia-related changes (AML-MRC) are limited. Our study examines the genetic profile of 118 RUNX1^mut AML patients including 57 AML with RUNX1^mut and 61 AML-MRC with RUNX1^mut and 100 AML, NOS patients with wild type RUNX1 (RUNX1^wt). Results revealed that AML-MRC patients with RUNX1^mut had shorter median overall survival (OS) (11 ± 3.3 months) when compared to AML with RUNX1^mut (19 ± 7.1 months) and AML, NOS with RUNX1^wt (not reached) (p = .001). The most common concurrent mutations observed in AML-MRC with RUNX1^mut patients were DNMT3A, SRSF2, ASXL1, and IDH2 while in AML with RUNX1^mut patients were ASXL1, SRSF2, TET2, IDH2, and DNMT3A. ASXL1 and TET2 mutations appeared to adversely affect OS in AML-MRC, but not in AML with RUNX1^mut. Concurrent RUNX1/DNMT3A mutations, in contrast had negative impact on OS in AML with RUNX1^mut, but not in AML-MRC with RUNX1^mut.

Keywords:

• RUNX1
• AML
• AML-MRC
• NGS

Author contributions

Conception and design: L.N., L.Z.

Collection and assembly of data: L.N., X.Z., K.M., E.R., S.Y., I.A., J.S., D.B., D.Q., D.A.S., J.E.L., A.F.L, L.C.M., E.P, L.Z.

Data analysis and interpretation: L.N., X.Z., S.Y., L.Z.

Manuscript writing: All authors participated in manuscript writing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported in part by a research grant from the Graduate Medical Education (GME) at the University of South Florida (S.Y. and L.Z.), a Research Training Award for Fellow (RTAF) from the American Society of Hematology (S.Y.), and by NIH [grant K08 CA237627] (S.Y.).