Interrogation of molecular profiles can help in differentiating between MDS and AML with MDS-related changes.

A subset of AML with myelodysplastic syndrome (MDS)-related changes (MRCs) occurs without a documented MDS phase. We studied genomic profile of 646 patients: 310 with MDS, 167 with AML without (w/o) MRC, 99 with primary (p) AML-MRC, and 70 with secondary (s) AML-MRC and sought to find differences in mutational patterns. Among the 32-myeloid associated genes studied, SF3B1 ( p  ≤ .001) was significantly mutated in higher proportion of patients with MDS, compared to other categories. NPM1 ( p  < .001), FLT3 ITD ( p  = .08), and NRAS ( p  = .02) mutations showed trend toward significance for AML w/o MRC, compared to other categories. In pAML-MRC, TP53 ( p  < .001) was significantly mutated in higher proportion of patients. Similarly, SETBP1 ( p  = .001), RUNX1 ( p  = .004), and SRSF2 ( p  = .04) mutations were more commonly seen in sAML-MRC. While these signatures may not be diagnostically discriminatory, they may help in disease categorization when other data are absent or in challenging cases.