| General information | Literature | Expression | Regulation | Mutation | Interaction |
|
Basic Information |
|
|---|---|
Gene ID | 10019 |
Name | SH2B3 |
Synonymous | IDDM20|LNK;SH2B adaptor protein 3;SH2B3;SH2B adaptor protein 3 |
Definition | SH2B adapter protein 3|lymphocyte-specific adapter protein Lnk|signal transduction protein Lnk |
Position | 12q24 |
Gene type | protein-coding |
|
Title |
Abstract |
| Genetic loss of SH2B3 in acute lymphoblastic leukemia. | The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL. Moreover, extended mutation analysis showed homozygous somatic mutations in SH2B3 in 2 of 167 ALLs analyzed. Overall, these results demonstrate a Knudson tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis. |