Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG).
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Ozga Michael, Nicolet Deedra, Mrózek Krzysztof, Yilmaz Ayse S, Kohlschmidt Jessica, Larkin Karilyn T, Blachly James S, Oakes Christopher C, Buss Jill, Walker Christopher J, Orwick Shelley, Jurinovic Vindi, Rothenberg-Thurley Maja, Dufour Annika, Schneider Stephanie, Sauerland Maria Cristina, Görlich Dennis, Krug Utz, Berdel Wolfgang E, Woermann Bernhard J, Hiddemann Wolfgang, Braess Jan, Subklewe Marion, Spiekermann Karsten, Carroll Andrew J, Blum William G, Powell Bayard L, Kolitz Jonathan E, Moore Joseph O, Mayer Robert J, Larson Richard A, Uy Geoffrey L, Stock Wendy, Metzeler Klaus H, Grimes H Leighton, Byrd John C, Salomonis Nathan, Herold Tobias, Mims Alice S, Eisfeld Ann-Kathrin
Аннотация
Clinical outcome of patients with acute myeloid leukemia (AML) is associated with demographic and genetic features. Although the associations of acquired genetic alterations with patients' sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols. A validation cohort comprised 465 women and 489 men treated on frontline protocols of the German AML Cooperative Group. Compared with men, women more often had normal karyotype, FLT3-ITD, DNMT3A, NPM1 and WT1 mutations and less often complex karyotype, ASXL1, SRSF2, U2AF1, RUNX1, or KIT mutations. More women were in the 2022 European LeukemiaNet intermediate-risk group and more men in adverse-risk group. We found sex differences in co-occurring mutation patterns and prognostic impact of select genetic alterations. The mutation-associated splicing events and gene-expression profiles also differed between sexes. In patients aged <60 years, SF3B1 mutations were male-specific adverse outcome prognosticators. We conclude that sex differences in AML-associated genetic alterations and mutation-specific differential splicing events highlight the importance of patients' sex in analyses of AML biology and prognostication.