The cytokine receptor-like factor 2 (CRLF2) gene, located on chromosome Xp22.3 or Yp11.3, encodes cytokine receptor-like factors (CRLFs), which form heterodimers with IL-7Ra that receive and transmit signals from thymic stromal lymphopoietin and upregulated CRLF2 expression activates the Janus kinase/signal transducer and activator of transcription (JAK/STAT) or phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway to promote the occurrence and progression of leukemia (1–4). The gene discussed is CRLF2; the disease is leukemia.