JAK1 mutations are not frequent events in adult T-ALL: a GRAALL study.

摘要

Activating somatic mutations in Tyrosine Kinase (TK) genes are frequent events in haematological malignancies, when they can provide promising therapeutic targets (Loriaux et al, 2008; Scholl et al, 2008). Somatic mutations of JAK1, a Janus Kinase (JAK) family member which plays important roles in normal and neoplastic haematopoiesis, were reported in 2/94 adult de-novo acute myeloid leukaemia (AML) (Xiang et al, 2008). Flex et al.(2008) reported JAK1 mutations in acute lympho-blastic leukaemia (ALL), particularly in adult T lineage cases, where the mutation rate was 8/38 (21%). Mutations were found within the SH2 (exon 10), Pseudo-Tyr-Kinase (exons 13 and 15) and the Tyr-Kinase (exon 18) domains of JAK1, with 6/8 mutations occurring in exons 15 and 18. The structural and functional consequences of these mutations was variable in molecular modelling and in-vitro assays (Flex et al, 2008).