• What is JAK2?
  • JAK2 in Acute Lymphoblastic Leukemia
  • JAK2 c.2047A>G (R683G)
  • Clinical Trials

JAK2

Janus kinase 2 (JAK2) encodes for a protein tyrosine kinase involved in cytokine receptor signaling. Mutations in JAK2 have been identified in ALL and other hematologic malignancies.

Preclinical models have been used to test efficacy of mTOR and JAK inhibitors in CRLF2-rearranged and JAK2-mutated high-risk precursor B-cell ALL (Maude et al. 2011).

Related Pathways

Contributors: Valerie Brown, M.D., Ph.D., Scott C. Borinstein, M.D., Ph.D., Debra Friedman, M.D.

Suggested Citation: Brown, V., S. Borinstein, D. Friedman. 2018. JAK2. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-lymphoblastic-leukemia/jak2/?tab=0 (Updated April 3).

Last Updated: April 3, 2018

JAK2 in Acute Lymphoblastic Leukemia

JAK2 is mutated in 85% of BCR-ABL1-negative, high-risk B-cell precursor pediatric ALL patients (Mullighan et al. 2009). It is mutated in 4-9% of B-cell precursor ALL, overall (Chen et al 2012; COSMIC​).

Most of the observed JAK2 mutations are thought to result in enhanced JAK2 kinase activity (Mullighan et al. 2009). JAK2 mutations are associated with higher risk of relapse (Mullighan et al. 2009).

Preclinical models have been used to test efficacy of mTOR and JAK inhibitors in CRLF2-rearranged and JAK2-mutated high-risk precursor B-cell ALL (Maude et al. 2011).

Contributors: Valerie Brown, M.D., Ph.D., Scott C. Borinstein, M.D., Ph.D., Debra Friedman, M.D.

Suggested Citation: Brown, V., S. Borinstein, D. Friedman. 2014. JAK2 in Acute Lymphoblastic Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-lymphoblastic-leukemia/jak2/ (Updated August 8).

Last Updated: August 8, 2014

JAK2 c.2047A>G (R683G) Mutation in Acute Lymphoblastic Leukemia

Properties
Location Exon 16 (coding exon 14), pseudokinase domain (Ensembl; Mullighan et al. 2009)
Frequency of JAK2 mutation in B-cell precursor ALL 4-9% (Chen et al 2012; COSMIC)
Frequency of R683G mutation among JAK2-mutated B-cell precursor ALL 32% (COSMIC)
Implications for Targeted Therapeutics
Response to PI3K/mTOR inhibitors Unknown at this timea
Response to JAK inhibitors Unknown at this timeb

The R683G mutation results in an amino acid substitution at position 683 in JAK2, from an arginine (R) to a glycine (G).

a In preclinical in vivo models, the mTOR inhibitor sirolimus inhibitied PI3K/mTOR signaling (Maude et al. 2011; Tasian et al. 2012).

b In preclinical in vivo models, the JAK inhibitor ruxolitinib (INCB018424) inhibited JAK/STAT signaling and reduced overall disease burden (Maude et al. 2011; Tasian et al. 2012).

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Contributors: Valerie Brown, M.D., Ph.D., Scott C. Borinstein, M.D., Ph.D., Debra Friedman, M.D.

Suggested Citation: Brown, V., S. Borinstein, D. Friedman. 2017. JAK2 c.2047A>G (R683G) Mutation in Acute Lymphoblastic Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-lymphoblastic-leukemia/jak2/200/ (Updated January 13).

Last Updated: January 13, 2017

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