Association of mutations with morphological dysplasia in acute myeloid leukemia without 2016 WHO Classification-defined cytogenetic abnormalities.

Despite improvements in our understanding of the molecular basis of acute myeloid leukemia (AML), the association between genetic mutations with morphological dysplasia remains unclear. In this study, we evaluated and scored dysplasia in bone marrow (BM) specimens from 168 patients with AML; none of these patients had cytogenetic abnormalities according to the 2016 World Health Organization Classification. We then performed targeted sequencing of diagnostic BM aspirates for recurrent mutations associated with myeloid malignancies. We found that cohesin pathway mutations [q (FDR-adjusted )=0.046] were associated with a higher degree of megakaryocytic dysplasia and mutations were marginally associated with greater myeloid lineage dysplasia (q=0.052). Frequent megakaryocytes with separated nuclear lobes were more commonly seen among cases with cohesin pathway mutations (q=0.010) and specifically in those with mutations (q=0.010), as well as mutations (q=0.022 when considering the presence of any no megakaryocytes with separated nuclear lobes). RAS pathway mutations (q=0.006) and (q=0.006) were significantly more frequent in cases without evaluable erythroid cells. In univariate analysis of the 153 patients treated with induction chemotherapy, mutations were associated with longer event-free survival (EFS) (=0.042), while (=0.042), (=0.040), frequent micromegakaryocytes (=0.018) and presence of a subclone (=0.002) were associated with shorter EFS. In multivariable modeling, was associated with longer EFS, while presence of a subclone and frequent micromegakaryocytes remained significantly associated with shorter EFS.