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慢性粒细胞白血病中bcr-abl转录本的可变5'端。

Alternative 5' end of the bcr-abl transcript in chronic myelogenous leukemia.

作者信息

Romero P, Beran M, Shtalrid M, Andersson B, Talpaz M, Blick M

机构信息

Department of Clinical Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.

出版信息

Oncogene. 1989 Jan;4(1):93-8.

PMID:2915904
Abstract

Philadelphia chromosome positive acute lymphocytic leukemia and chronic myelogenous leukemia are strongly associated with two distinct forms of bcr-abl chimeric protein, known as P190 and P210, respectively. By studying cDNA clones obtained from the cell line KBM-5, we identified two new bcr-abl transcripts. These are formed by alternative splicing of at least two exons to the known bcr exon 2. One novel transcript can encode a protein kinase of approximately 190 kd, while the other can direct the synthesis of a larger protein whose amino terminus remains to be defined. The alternative exons can be spliced also to the two normal bcr transcripts, reflecting the activation of a cryptic promoter. These messages were present at low abundance in two cases of blastic crisis but were not detected in the chronic phase. It is conceivable that the proteins encoded by the new bcr-abl mRNAs are involved in the transformation to the acute phase in some cases of chronic myelogenous leukemia.

摘要

费城染色体阳性急性淋巴细胞白血病和慢性粒细胞白血病分别与两种不同形式的bcr-abl嵌合蛋白密切相关,这两种蛋白分别称为P190和P210。通过研究从细胞系KBM-5获得的cDNA克隆,我们鉴定出两种新的bcr-abl转录本。它们是由至少两个外显子与已知的bcr外显子2进行可变剪接形成的。一种新的转录本可以编码一种约190kd的蛋白激酶,而另一种则可以指导合成一种更大的蛋白,其氨基末端尚待确定。这些可变外显子也可以与两种正常的bcr转录本进行剪接,这反映了一个隐蔽启动子的激活。这些信息在两例急变期病例中低丰度存在,但在慢性期未检测到。可以想象,新的bcr-abl mRNA编码的蛋白质在某些慢性粒细胞白血病病例向急性期的转化中起作用。

相似文献

1
Alternative 5' end of the bcr-abl transcript in chronic myelogenous leukemia.慢性粒细胞白血病中bcr-abl转录本的可变5'端。
Oncogene. 1989 Jan;4(1):93-8.
2
Acute lymphoid leukemia molecular phenotype in a patient with benign-phase chronic myelogenous leukemia.一名处于良性期慢性粒细胞白血病患者的急性淋巴细胞白血病分子表型
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Novel types of bcr-abl transcript with breakpoints in BCR exon 8 found in Philadelphia positive patients with typical chronic myeloid leukemia retain the sequence encoding for the DBL- and CDC24 homology domains but not the pleckstrin homology one.在典型慢性髓性白血病的费城染色体阳性患者中发现的新型bcr-abl转录本,其断点位于BCR外显子8,保留了编码DBL和CDC24同源结构域的序列,但不保留pleckstrin同源结构域的序列。
Haematologica. 2002 Jul;87(7):688-94; discussion 694.
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Is p190 bcr-abl rearrangement necessary for acute transformation in some p210 CML of childhood?在儿童某些p210慢性粒细胞白血病(CML)中,p190 bcr-abl重排对于急性转化是否必要?
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Alternative BCR/ABL splice variants in Philadelphia chromosome-positive leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approaches.费城染色体阳性白血病中的替代性BCR/ABL剪接变体可产生新的肿瘤特异性融合蛋白,这些蛋白可能是免疫治疗方法的潜在靶点。
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Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein.一种表达p230 BCR/ABL融合蛋白的费城染色体新型白血病细胞系的建立及分子特征分析
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[Molecular analysis of transformation into blast crisis in chronic myelogenous leukemia].[慢性粒细胞白血病向急变期转化的分子分析]
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Alu and translisin recognition site sequences flanking translocation sites in a novel type of chimeric bcr-abl transcript suggest a possible general mechanism for bcr-abl breakpoints.一种新型嵌合bcr-abl转录本中易位位点侧翼的Alu和转座酶识别位点序列提示了bcr-abl断点的一种可能的普遍机制。
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Coexistence of different clonal populations harboring the b3a2 (p210) and e1a2 (p190) BCR-ABL1 fusion transcripts in chronic myelogenous leukemia resistant to imatinib.在对伊马替尼耐药的慢性粒细胞白血病中存在携带b3a2(p210)和e1a2(p190)BCR-ABL1融合转录本的不同克隆群体。
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Cancer Res. 1993 Aug 1;53(15):3603-10.

引用本文的文献

1
Exon-skipping in BCR/ABL is induced by ABL exon 2.BCR/ABL中的外显子跳跃由ABL外显子2诱导。
Biochem J. 2000 May 15;348 Pt 1(Pt 1):63-9.
2
Progressive de novo DNA methylation at the bcr-abl locus in the course of chronic myelogenous leukemia.慢性粒细胞白血病病程中bcr-abl基因座的渐进性新生DNA甲基化。
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10722-6. doi: 10.1073/pnas.91.22.10722.
3
New nucleotide sequence data on the EMBL File Server.欧洲分子生物学实验室文件服务器上的新核苷酸序列数据。
Nucleic Acids Res. 1990 Feb 11;18(3):695-700. doi: 10.1093/nar/18.3.695.