期刊
BLOOD
卷 97, 期 12, 页码 3910-3918出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.V97.12.3910
关键词
-
类别
资金
- NCI NIH HHS [P01 CA66996-01] Funding Source: Medline
- PHS HHS [P01 OK50654] Funding Source: Medline
The molecular cloning of the t(5;10)(q33; q22) associated with atypical chronic myeloid leukemia (CML) is reported. Fluorescence in situ hybridization (FISH), Southern blot, and reverse transcriptase-polymerase chain reaction analysis demonstrated that the translocation resulted in an H4/platelet-derived growth factor receptor betaR (PDGF betaR) fusion transcript that incorporated 5 ' sequences from H4 fused in frame to 3 ' PDGF betaR sequences encoding the transmembrane, WW-like, and tyrosine kinase domains. FISH combined with immunophenotype analysis showed that t(5;10)(q33;q22) was present in CD13(+) and CD14(+) cells but was not observed in CD3(+) or CD19(+) cells. H4 has previously been implicated in pathogenesis of papillary thyroid carcinoma as a fusion partner of RET, The H4/RET fusion incorporates 101 amino acids of H4, predicted to encode a leucine zipper dimerization domain, whereas the H4/PDGF betaR fusion incorporated an additional 267 amino acids of H4, Retroviral transduction of H4/PDGF betaR, but not a kinase-inactive mutant, conferred factor-independent growth to Ba/F3 cells and caused a T-cell lymphoblastic lymphoma in a murine bone marrow transplantation assay of transformation. Mutational analysis showed that the amino-terminal H4 leucine zipper domain (amino acids 55-93), as well as H4 amino acids 101 to 386, was required for efficient induction of factor-independent growth of Ba/F3 cells. Tryptophan-to-alanine substitutions in the PDGF betaR WW-like domain at positions 566/593, or tyrosine-to-phenylalanine substitutions at PDGF betaR positions 579/581 impaired factor-independent growth of Ba/F3 cells. H4/PDGF betaR is an oncoprotein expressed in t(5;10)(q33;q22) atypical CML and requires dimerization motifs in the H4 moiety, as well as residues implicated in signal transduction by PDGFPR, for efficient induction of factor-independent growth of Ba/F3 cells, (C) 2001 by The American Society of Hematology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据