1p31.3

AIIDE,JAK1A,JAK1B,JTK3

Acute lymphoblastic leukemia T cell type (T-ALL) and Acute lymphoblastic leukemia B cell type (B-ALL)

JAK1 mutations are associated with advanced age, poor response to therapy and overall prognosis (Flex et al., 2008).

Somatic JAK1 mutations occur in T cell acute lymphoblastic leukemia (ALL). These mutations seem to be more frequent among adult T-ALL patients, but the frequency varies between studies: 8/38 (21.0%; adult; Flex et al., 2008), 1/49 (2.0%; children; Flex et al., 2008), 2/11 (27.3%; adult; Jeong et al., 2008), 4/108 (3.7%; adult; Asnafi et al., 2009). These mutations represent gain of function mutations that participate in the leukemogenic process by inducing the constitutive activation of the JAK-STAT pathway.
Amino acid substitutionProof of hyperactivitydomainreference

R724H	Yes	Pseudokinase	Flex et al., 2008
V658F	Yes	Pseudokinase	Mullighan et al., 2009

JAK1 mutations were found in 3 B-cell ALL samples after the resequencing of 173 B-ALL (Flex et al., 2008) and in 3 samples after the resequencing of 187 high risk childhood B-ALL (Mullighan et al., 2009). No mutations were found after the resequencing of 69 B-ALL (Jeong et al., 2008).
L624_R629>WYesPseudokinaseMullighan et al., 2009 JAK1 mutants induce the activation of different cytokine-receptor complexes like the IL-9 receptor or the IL-2 receptor, that will induce the constitutive activation of the JAK-STAT pathway.

Acute myeloid leukemia (AML)

JAK1 mutations were found in two AML samples after the resequencing of 94 AML (Xiang et al., 2008) and in one AML sample after the resequencing of 105 AML.
Amino acid substitutionProof of hyperactivitydomainreference

V623A		Pseudokinase	Xiang et al., 2008
V658F	Yes	Pseudokinase	Jeong et al., 2008

Hepatocellular carcinoma

JAK1 mutations were found in one hepatocellular carcinoma sample after the screening of 84 hepatocellular carcinoma.
Amino acid substitutionProof of hyperactivitydomainreference

Q644H;V645F

Pseudokinase

Xie et al., 2009

Breast cancer

JAK1 mutation was found in a breast cancer sample after the resequencing of 90 breast cancers.
Table 5: Somatic mutations in JAK1 found in breast cancer samples.

Amino acid substitution	Proof of hyperactivity	domain	reference
H647Y		Pseudokinase	Jeong et al., 2008

Non-small cell lung cancer

JAK1 mutation was found in a non-small cell lung cancer sample after the resequencing of 47 non-small cell lung cancer samples.
Table 6: Somatic mutations in JAK1 found in non-small cell lung cancer samples.

Amino acid substitution	Proof of hyperactivity	domain	reference
P782M		Pseudokinase	Jeong et al., 2008