• What is CRLF2?
  • CRLF2 in Acute Lymphoblastic Leukemia
  • CRLF2 c.695T>G (F232C)
  • 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 c.695T>G (F232C) Mutation in Acute Lymphoblastic Leukemia

Properties
Location Exon 6 (Ensembl)
Frequency of CRLF2 mutation in B-cell precursor ALL 2% (Chen et al. 2012)
Frequency of F232C mutation among CRLF2-mutated B-cell precursor ALL 100% (Chen et al. 2012)
Implications for Targeted Therapeutics
Response to PI3K/mTOR inhibitors Unknown at this time
Response to JAK inhibitors Unknown at this time

The F232C mutation results in an amino acid substitution at position 232 in CRLF2, from a phenylalanine (F) to a cysteine (C).

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 c.695T>G (F232C) Mutation in Acute Lymphoblastic Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-lymphoblastic-leukemia/crlf2/199/ (Updated February 18).

Last Updated: February 18, 2015

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