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Publication : Targeting beta2-microglobulin for induction of tumor apoptosis in human hematological malignancies.

First Author  Yang J Year  2006
Journal  Cancer Cell Volume  10
Issue  4 Pages  295-307
PubMed ID  17045207 Mgi Jnum  J:114975
Mgi Id  MGI:3690495 Doi  10.1016/j.ccr.2006.08.025
Citation  Yang J, et al. (2006) Targeting beta2-microglobulin for induction of tumor apoptosis in human hematological malignancies. Cancer Cell 10(4):295-307
abstractText  We discovered that monoclonal antibodies (mAbs) specific to human beta(2)-microglobulin (beta(2)M) induce apoptosis in vitro and were therapeutic in mouse models of myeloma and other hematological tumor cells. Cell death occurred rapidly, without the need for exogenous immunological effector mechanisms. The mAbs induced cell death via recruiting MHC class I molecules to lipid rafts and activating Lyn and PLCgamma2, leading to activated JNK and inhibited PI3K/Akt and ERK, compromised mitochondrial integrity, and caspase-9-dependent cascade activation. Although the expression of beta(2)M on normal hematopoietic cells is a potential safety concern, the mAbs were selective to tumor-transformed cells and did not induce apoptosis of normal cells. Therefore, such mAbs offer the potential for a therapeutic approach to hematological malignancies.
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