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Anti-cd44 Antibody Of Fresh Acute Myeloid Induced Apoptosis Of Leukemia Cell Differentiation And Its Single-chain Antibody Construct

Posted on:2005-02-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:G L SongFull Text:PDF
GTID:1114360185473358Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
BackgroundAcute myeloid leukemia (AML) is the most common type of acute leukemia in adults. It is a heterogeneous neoplasm characterized by the accumulation of leukemia blast arrested at various stages of granulocytic and monocytic differentiation. As conventional chemotherapy does not seem to be effective to cure most AML patients, there has been an effort to find new drugs that possess differentiative and apoptotic potentials. CD44 antigen is a highly glycosylated transmembrane protein that expresses on leukemia blasts in all acute myeloid leukemia (AML) subtypes. Because CD44 is a signaling receptor that plays an important role in myelopoiesis, it may be used as a target molecule to induce terminal differentiation and apoptosis in AML cells. It has been reported that ligation of CD44 with some specific anti-CD44 monoclonal antibodies can reverse the differentiation blockage of leukemia cell lines. In this study, the differentiation and apoptosis-inducing effects of HI44a, another anti-CD44 monoclonal antibody, were investigated on leukemia cells obtained from patients with AML-M2, AML-M3, AML-M4 or AML-M5 and on THP-1 cells. As the mouse antibodies are restricted in clinical use due to their high immunogenecity, we constructed a recombinant antibody by genetic engineering to minimize the human anti-mouse antibody response. Methods...
Keywords/Search Tags:Differentiation
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