Study results from University of California, Division of Hematology in the area of myeloproliferative disorders published
2007 NOV 19 -- Scientists discuss in 'Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders' new findings in myeloproliferative disorders. According to recent research from the United States, "Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells." "The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk in UT7-MPLW515L cells enhances proliferation. Lnk blocks the activation of Jak2, Stat3, Erk, and Akt in these cells. Furthermore, MPLW515L-expressing cells are more susceptible to Lnk inhibitory functions than their MPL wild-type (MPLWT)-expressing counterparts. Lnk associates with activated MPLWT and MPLW515L and colocalizes with the receptors at the plasma membrane. The SH2 domain of Lnk is essential for its binding and for its down-regulation of MPLWT and MPLW515L. Lnk itself is tyrosine-phosphorylated following thrombopoietin stimulation," wrote S. Gery and colleagues, University of California, Division of Hematology. The researchers concluded: "Further elucidating the cellular pathways that attenuate MPLW515L will provide insight into the pathogenesis of MPD and could help develop specific therapeutic approaches." Gery and colleagues published their study in Blood (Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders. Blood, 2007;110(9):3360-4). For additional information, contact S. Gery, Oncology, Division of Hematology, UCLA School of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048 USA.. Publisher contact information for the journal Blood is: American Society Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA. Keywords: United States, Los Angeles, Hematology, Myeloproliferative Disorders, Oncology. This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2007, Clinical Oncology Week via NewsRx.com.
|
