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[慢性粒细胞白血病和急性淋巴细胞白血病中bcr-abl基因的重排与表达]

[Rearrangement and expression of bcr-abl genes in CML and ALL].

作者信息

Kunieda Y, Okabe M

机构信息

Third Department of Internal Medicine, Hokkaido University School of Medicine.

出版信息

Rinsho Ketsueki. 1991 Jun;32(6):623-8.

PMID:1890738
Abstract

We have carried out the molecular and cell-biological analysis on Ph1-positive leukemias in this study. Five out of nine Ph1-positive ALL cases showed molecular rearrangement within the classical bcr sequence (or M-bcr), similar as those in 47 CML cases. We examined 4 cases of Ph1-positive ALL presenting no rearrangement of M-bcr and found that, in 2 of 4 cases, one showed the breakpoint in a 5 kb segment of the bcr gene first intron (bcr-2) and the other in bcr-1, 16 kb upstream of bcr-2. Ph1-positive ALL frequently showed biphenotypical or biclonal phenotypes of myeloid and lymphoid lineages. Furthermore, we demonstrated the ability of two Ph1-positive ALL cell lines to differentiate into monocytic lineage in vitro, thus suggesting the possibility that these Ph1-positive ALL cells might reside on the stage of multipotent stem cell along the hematopoietic cell differentiation. Two out of 31 CML cases showed the mutations of the ras genes by the polymerase chain reaction; one case in the crisis phase and the other in the chronic phase. However, no mutations of the fms genes was detected. Two cases in the crisis phase of 24 CML patients (11 cases in the chronic phase and 13 cases in the crisis phase) contained rearrangements of the p53 gene by Southern analysis. Furthermore, the transcriptional alteration was found in 2 CML-BC and 2 CML-BC derived cell lines' samples, suggesting a important role of the p53 gene in the transformation of CML into the crisis phase.

摘要

在本研究中,我们对Ph1阳性白血病进行了分子和细胞生物学分析。9例Ph1阳性急性淋巴细胞白血病(ALL)病例中有5例在经典bcr序列(或M-bcr)内出现分子重排,与47例慢性髓性白血病(CML)病例相似。我们检查了4例未发生M-bcr重排的Ph1阳性ALL病例,发现其中2例,1例在bcr基因第一内含子的5 kb片段(bcr-2)出现断点,另1例在bcr-1出现断点,bcr-1位于bcr-2上游16 kb处。Ph1阳性ALL常表现为髓系和淋巴系的双表型或双克隆表型。此外,我们证明了2株Ph1阳性ALL细胞系在体外具有分化为单核细胞系的能力,因此提示这些Ph1阳性ALL细胞可能处于造血细胞分化过程中多能干细胞阶段。31例CML病例中有2例通过聚合酶链反应检测到ras基因突变;1例处于急变期,另1例处于慢性期。然而,未检测到fms基因的突变。24例CML患者(11例慢性期和13例急变期)中有2例急变期病例通过Southern分析发现p53基因重排。此外,在2例CML急变期(CML-BC)及2例CML-BC来源的细胞系样本中发现转录改变,提示p53基因在CML向急变期转化中起重要作用。

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