Angenendt L, Röllig C, Montesinos P, et al. - Regardless of accompanying cytogenetic abnormalities, the 2017 European LeukemiaNet guidelines assume the association of nucleophosmin 1 (NPM1) mutations with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITD^neg) or present with a low allelic ratio (FLT3-ITD^low), researchers examined whether this assumption is valid via examining correlations between karyotype and outcome in intensively treated patients with NPM1^mut/FLT3-ITD^neg/low AML. From registry databases from nine international study groups or treatment centers, they assessed 2,426 patients with NPM1^mut/FLT3-ITD^neg/low AML. Of these, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. Results indicated a significant association of karyotype abnormalities with outcome in NPM1^mut/FLT3-ITD^neg/low AML. Patients with NPM1^mut exhibited unfavorable prognosis comparable to those with NPM1 wild type when adverse-risk cytogenetics are present and hence, these should be classified and treated accordingly. Thus, predominance of cytogenetic risk over molecular risk was evident in NPM1^mut/FLT3-ITD^neg/low AML.