PMKB

Interpretation 3

Tier 2

Variants

Interpretation

Activating mutations in JAK1 (SH2-, pseudokinase -and kinase- domains) have been reported in approximately 5-20% of cases of T-Cell Acute Lymphoblastic Leukemia, in "Ph-like ALL" and in less than 5% of Acute Myeloid Leukemia. Some, but not all, of these mutations have been shown to be inhibitable by ATP-competitive JAK inhibitors or Type I interferon.

Citations

Flex E, et al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J Exp Med 2008;205(4):751-8
Aranaz P, et al. A new potential oncogenic mutation in the FERM domain of JAK2 in BCR/ABL1-negative and V617F-negative chronic myeloproliferative neoplasms revealed by a comprehensive screening of 17 tyrosine kinase coding genes. Cancer Genet Cytogenet 2010;199(1):1-8
Asnafi V, et al. JAK1 mutations are not frequent events in adult T-ALL: a GRAALL study. Br J Haematol 2010;148(1):178-9
Zhang J, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 2012;481(7380):157-63
Wang Q, et al. Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia. Haematologica 2011;96(12):1808-14
Hornakova T, et al. Oncogenic JAK1 and JAK2-activating mutations resistant to ATP-competitive inhibitors. Haematologica 2011;96(6):845-53
Hornakova T, et al. ALL-associated JAK1 mutations confer hypersensitivity to the antiproliferative effect of type I interferon. Blood 2010;115(16):3287-95
Mullighan CG, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 2009;106(23):9414-8
Xiang Z, et al. Identification of somatic JAK1 mutations in patients with acute myeloid leukemia. Blood 2008;111(9):4809-12
National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Acute Lymphoblastic Leukemia (Version 1.2018).

Last updated: 2019-08-28 14:54:00 UTC

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