RUNX1 point mutations potentially identify a subset of early immature T-cell acute lymphoblastic leukaemia that may originate from differentiated T-cells

• Published in: Gene Vol. 545; no. 1; pp. 111 - 116
• Main Authors: Mok, Michelle Meng Huang, Du, Linsen, Wang, Chelsia Qiuxia, Tergaonkar, Vinay, Liu, Te Chih, Yin Kham, Shirley Kow, Sanda, Takaomi, Yeoh, Allen Eng-Juh, Osato, Motomi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.07.2014
• Subjects: Adolescent; AML1; Cell Differentiation - genetics; Cell Line, Tumor; Child; Child, Preschool; Core Binding Factor Alpha 2 Subunit - genetics; Early immature T-ALL; ETP-ALL; Female; Genes, T-Cell Receptor gamma; Humans; Male; Point Mutation; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology; RUNX1; Sequence Deletion; TCRγ deletion; Young Adult; cCD3; TCR; Early immature T-ALL; ABD; TdT; CNV; sCD3; TCRγ deletion; RUNX1; AML1; RD; ETP-ALL; SNP; TAD; T-ALL; PCR; gDNA
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2014.04.074

The RUNX1/AML1 gene is among the most frequently mutated genes in human leukaemia. However, its association with T-cell acute lymphoblastic leukaemia (T-ALL) remains poorly understood. In order to examine RUNX1 point mutations in T-ALL, we conducted an amplicon-based deep sequencing in 65 Southeast Asian childhood patients and 20 T-ALL cell lines, and detected RUNX1 mutations in 6 patients (9.2%) and 5 cell lines (25%). Interestingly, RUNX1-mutated T-ALL cases seem to constitute a subset of early immature T-ALL that may originate from differentiated T-cells. This result provides a deeper insight into the mechanistic basis for leukaemogenesis. •RUNX1 is mutated in 6 of 65 T-ALL patients and 5 of 20 T-ALL cell lines.•RUNX1 mutation appears to be associated with early immature T-ALL subtype.•RUNX1-mutated T-ALL cells exhibit TCRγ deletion, a hallmark of mature T-cells.•Early immature T-ALL with RUNX1 mutation may originate from differentiated cells.