• What is CRLF2?
  • CRLF2 in Acute Lymphoblastic Leukemia
  • CRLF2 Fusions
  • Clinical Trials

CRLF2

Cytokine receptor-like factor 2 (CRLF2) encodes for a receptor protein that participates in activating STAT, possibly through JAK pathways. These pathways are important in immune system regulation. In cancer, CRLF2 rearrangements and one recurring mutation leading to CRLF2 overexpression have been identified in a subset of patients with high risk acute lymphoblastic leukemia who have an exceptionally dismal prognosis.

JAK and mTOR inhibitors have been explored in preclinical models as potential therapies targeting CRLF2-rearranged ALL (Maude et al. 2011; Tasian et al. 2012).

Related Pathways

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

Suggested Citation: Brown, V., D. Friedman, S. Borinstein. 2015. CRLF2. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-lymphoblastic-leukemia/crlf2/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

CRLF2 in Acute Lymphoblastic Leukemia

In B-cell precursor ALL, CRLF2 is rearranged in 30% of cases and has high expression in 17.5% of cases (Chen et al. 2012). CRLF2 fusion partners include P2RY8 and IGH (Chen et al. 2012; Mullighan et al. 2009). It is also sometimes mutated (Chen et al. 2012).

High CRLF2 expression independently is correlated with longer recurrence free survival in high-risk B-cell precursor ALL (Chen et al. 2012).

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; 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. 2015. CRLF2 in Acute Lymphoblastic Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-lymphoblastic-leukemia/crlf2/ (Updated June 10).

Last Updated: June 10, 2015

CRLF2 Fusions in Acute Lymphoblastic Leukemia

Properties
Location Chromosomal rearrangements involving the CRLF2 gene on Xp22.3 and Yp11.3
Frequency of CRLF2 fusions in B-cell precursor ALL 31% (Chen et al 2012)
Implications for Targeted Therapeutics
Response to PI3K/mTOR inhibitors Unknown at this timea
Response to JAK inhibitors Unknown at this timeb

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).

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. CRLF2 Fusions in Acute Lymphoblastic Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-lymphoblastic-leukemia/crlf2/208/ (Updated August 8).

Last Updated: August 8, 2014

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