The new provisional WHO entity ‘RUNX1 mutated AML’ shows specific genetics but no prognostic influence of dysplasia

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

“…However, whether clinical outcome of AML-MRC with RUNX1 mut is worse than AML with RUNX1 mut is yet unknown and there has been debate regarding prognostic impact of multilineage dysplasia in AML patients with RUNX1 mut . Similar to a previous study reported by Haferlach's group [20], mild morphologic dysplasia in hematopoietic precursor did not adversely affect the clinical outcome in our patient with AML with RUNX1 mut or AML-MRC with RUNX1 mut (data not shown). However, we observed that AML-MRC with RUNX1 mut is associated with inferior OS compared to AML with RUNX1 mut .…”

“…Recent studies have demonstrated that AML with RUNX1 mut has a unique cytogenetic signature [20,28]. Trisomy 13 is reportedly strongly associated with RUNX1 mutation in AML (9%, 13/152) [20,29]. However, the presence of trisomy 13 was extremely low in our study appearing only in 5.9% and 3.3% of patients with AML with RUNX1 mut and AML-MRC with RUNX1 mut , respectively.…”

“…Recent studies have demonstrated that AML with RUNX1 mut has a unique cytogenetic signature [20,28]. Trisomy 13 is reportedly strongly associated with RUNX1 mutation in AML (9%, 13/152) [20,29].…”

Overexpression of RUNX1 short isoform has an important role in the development of myelodysplastic/myeloproliferative neoplasms

“…3 The biological function of these mutations has been elucidated in a mouse model 4 and in human CD34…”

NPM1 mutation but not RUNX1 mutation or multilineage dysplasia defines a prognostic subgroup within de novo acute myeloid leukemia lacking recurrent cytogenetic abnormalities in the revised 2016 WHO classification

“…1 In the context of altered definitions in the revised WHO classification, the prognostic significance of the mutation-defined AML-RGA entities relative to AML-NOS and AML-MRC is uncertain. [2][3][4] We assessed the ability of the revised 2016 WHO AML categories to predict prognosis within a cohort of patients with clinically-defined de novo AML lacking WHO-defined recurrent cytogenetic abnormalities.…”