| General information | Literature | Expression | Regulation | Mutation | Interaction |
Basic Information | |
|---|---|
Gene ID | 3574 |
Name | IL7 |
Synonymous | IL-7;interleukin 7;IL7;interleukin 7 |
Definition | interleukin-7 |
Position | 8q12-q13 |
Gene type | protein-coding |
Cancer type | Abstract |
| acute lymphoblastic leukemia;Hematological | Interleukin 7 (IL-7) and its receptor, formed by IL-7Ralpha (encoded by IL7R) and gammac, are essential for normal T-cell development and homeostasis. Here we show that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL).We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon 6 mutations. In most cases, these IL7R mutations introduce an unpaired cysteine in the extracellular juxtamembrane-transmembrane region and promote de novo formation of intermolecular disulfide bonds between mutant IL-7Ralpha subunits, thereby driving constitutive signaling via JAK1 and independently of IL-7, gammac or JAK3. IL7R mutations induce a gene expression profile partially resembling that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3 rearranged and HOXA deregulated cases. Notably, IL7R mutations promote cell transformation and tumor formation. Overall, our findings indicate that IL7R mutational activation is involved in human T-cell leukemogenesis, paving the wayfor therapeutic targeting of IL-7R-mediated signaling in T-ALL. |