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Updated: Jun 17, 2026
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A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules
Published on: March 10, 2017
Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia.
Akinori Yoda1, Yuka Yoda, Sabina Chiaretti
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Summary
Cytokine receptor CRLF2 is overexpressed in B-cell acute lymphoblastic leukemia (B-ALL), driving poor prognosis. Targeting CRLF2 and JAK signaling offers new therapeutic strategies for B-ALL patients.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Precursor B-cell acute lymphoblastic leukemia (B-ALL) in adults has a poor prognosis due to limited therapeutic targets.
- Identifying novel molecular drivers is crucial for improving B-ALL treatment outcomes.
Purpose of the Study:
- To identify novel therapeutic targets in B-ALL.
- To investigate the role of CRLF2 in B-ALL pathogenesis and its potential as a therapeutic target.
Main Methods:
- Functional screening of B-ALL-derived mRNA transcripts.
- Analysis of CRLF2 and JAK2 expression and mutation status in B-ALL patient samples.
- Investigating the signaling pathways involved in CRLF2-mediated growth.
Main Results:
- CRLF2 is overexpressed in ~15% of adult and high-risk pediatric B-ALL, associated with poor prognosis.
- CRLF2 overexpression results from IGH translocations or deletions and activates JAK-STAT signaling.
- Activating mutations in JAK2 mutually exclusive with CRLF2 mutations, with CRLF2 acting as a scaffold for mutant JAK2 signaling.
- CRLF2-dependent cells are sensitive to JAK and PKC inhibitors.
Conclusions:
- CRLF2 is a key factor in a subset of B-ALL, serving as a diagnostic and prognostic marker.
- Targeting CRLF2 and associated signaling pathways presents a promising therapeutic strategy for B-ALL.
