Association of a single-nucleotide polymorphism in the SH2B3 gene with JAK2V617F-positive myeloproliterative neoplasms

摘要

In a recent paper, Perez-Garcia et al described an inherited mutation in the SH2B3 gene associated with the development of acute lymphoblastic leukemia. SH2B3 encodes the lymphocyte adaptor protein (LNK) that negatively modulates the signaling of several cytokine receptors, including the thrombopoietin receptor (myelo-proliferative leukemia virus oncogene [MPL]) and the erythropoietin receptor, by attenuating JAK2 kinase activation. LNK was also shown to bind and regulate mutant signaling molecules found in myeloproliferative neoplasms (MPNs) like MPL-W515L and JAK2-V617F through its SH2 domain and a novel site at its amino-terminal region. Lastly, several acquired SH2B3 mutations in the pleckstrin homology domain and NH2-terminal region of the protein were reported in MPNs.