alexa RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular Biomarkers & Diagnosis

Author(s): Schnittger S, Dicker F, Kern W, Wendland N, Sundermann J,

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Abstract Analyses of 164 RUNX1 mutations (RUNX1mut) in 147 of 449 patients (32.7\%) with normal karyotype or noncomplex chromosomal imbalances were performed. RUNX1mut were most frequent in acute myeloid leukemia French-American-British classification M0 (65.2\%) followed by M2 (32.4\%) and M1 (30.2\%). Considering cytogenetics, RUNX1mut were most frequent in cases with +13 (27 of 30, 90\%), whereas frequencies were similar in other cytogenetic groups (26\%-36\%). The molecular genetic markers most frequently associated with RUNX1mut were partial tandem duplication in the MLL gene (19.7\%), internal tandem duplication in the FLT3 gene (FLT3-ITD; 16.3\%), and NRAS mutations (9.5\%). Patients with RUNX1mut had shorter overall and event-free survival compared with RUNX1 wild-type cases (median, 378 days vs not reached, P = .003; and median, 285 vs 450 days, P = .003, respectively). In addition, it was shown that the adverse effect of RUNX1 was independent of the adverse effect of FLT3-ITD as well as of the high frequency of prognostically favorable NPM1mut and CEBPAmut in the RUNX1wt group. No effect of the type or localization of the individual RUNX1 mutations was observed. Multivariate analysis showed independent prognostic relevance for overall survival for RUNX1mut (P = .029), FLT3-ITD (P = .003), age (P < .001), and white blood cell count (P < .002). This article was published in Blood and referenced in Journal of Molecular Biomarkers & Diagnosis

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