The cytokine receptor-like factor 2 (CRLF2) is a transmembrane protein belonging to the type I cytokine receptor family, structurally homologous to receptors like thrombopoietin receptor (TPOR) and erythropoietin receptor (EPOR). It forms heterodimeric complexes, notably with the interleukin-7 receptor alpha (IL7Rα), to serve as a receptor for thymic stromal lymphopoietin (TSLP), a cytokine critical in T-cell maturation and allergic inflammation. CRLF2 gained prominence due to its pathogenic role in hematologic malignancies, particularly B-cell acute lymphoblastic leukemia (B-ALL). Aberrant CRLF2 expression, often caused by chromosomal rearrangements (e.g., P2RY8-CRLF2 or IGH-CRLF2 fusions) or mutations, leads to constitutive activation of JAK-STAT signaling, promoting leukemogenesis. Overexpression is frequently observed in high-risk B-ALL subtypes, including Philadelphia chromosome-like (Ph-like) ALL and Down syndrome-associated ALL.
Antibodies targeting CRLF2 are essential tools for diagnosing CRLF2-driven malignancies, detecting overexpression via flow cytometry or immunohistochemistry. They also aid in research to elucidate CRLF2 signaling mechanisms and evaluate therapeutic strategies, such as JAK inhibitors or CRLF2-directed biologics. Despite progress, challenges remain in understanding CRLF2's context-dependent roles in normal immunity versus oncogenesis, driving ongoing studies to optimize targeted therapies and overcome resistance.