Identification of two novel mutations in human acute myeloid leukemia cases

• Published in: Leukemia & lymphoma Vol. 62; no. 2; pp. 454 - 461
• Main Authors: O'Brien, Gráinne, Zyla, Joanna, Manola, Kalliopi N., Pagoni, Maria N., Polanska, Joanna, Badie, Christophe
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 28.01.2021
• Subjects: Acute myeloid leukemia; Cytogenetic Analysis; DNMT3A; genetic mutations; Humans; Karyotype; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - genetics; Mutation; Prognosis; RUNX1; genetic mutations; Acute myeloid leukemia; DNMT3A; RUNX1
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428194.2020.1832664

Acute myeloid leukemia (AML) is an aggressive cancer that progresses rapidly with a poor prognosis. Cytogenetic analysis provides the most accurate determination of diagnosis and prognosis however, about 42-48% of AML patients have a cytogenetically normal karyotype. Genetic analysis can provide further information and the identification of new mutations could result in improved risk stratification, prognosis and better understanding of the mechanisms of AML leukaemogenesis. In this study, we analyzed genetic alterations in 16 human AML cases by Haloplex sequencing with confirmation of two previously unreported mutations in the genes DNMT3A and RUNX1 by Sanger sequencing or pyrosequencing. The two novel mutations consist of two frameshift mutations identified in two different AML patients and reported as deleterious by bioinformatic analysis. These mutations confirm the exclusion and co-occurrence of specific gene mutation patterns in AML and may provide further information for patient diagnosis and prognosis.