Aberrant FHIT mRNA transcripts are present in malignant and normal haematopoiesis, but absence of FHIT protein is restricted to leukaemia

Aberrant FHIT mRNA transcripts are present in malignant and normal haematopoiesis, but absence of FHIT protein is restricted to leukaemia
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异常的 FHIT mRNA 转录物存在于恶性和正常造血系统中,但 FHIT 蛋白的缺失仅限于白血病

DOI:
10.1038/sj.onc.1202256
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发表时间:
1999
期刊:
影响因子:
8
通讯作者:
M. Fey
M. Fey
中科院分区:
医学1区
文献类型:
--
作者:
U. Peters;U. Hasse;E. Oppliger;M. Tschan;S. Ong;F. Rassool;B. Borisch;A. Tobler;M. Fey

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最近克隆的脆性组氨酸三联体(FHIT)基因在染色体3p14.2的变化是常见的各种实体瘤和癌细胞系。基于这些发现,FHIT被认为是一个假定的肿瘤抑制基因。我们评估了FHIT基因的mRNA表达的样本从55例各种血液恶性肿瘤(21 AML,8 CML,10 CLL,7个低级别和9个高级别的非霍奇金淋巴瘤),在一组16个白血病细胞系,在正常成熟的造血细胞的髓系和淋巴系,以及在CD 34+造血祖细胞。在14/16(88%)的白血病细胞系,43/55(78%)的原发性血液肿瘤,但也在17/22(77%)正常对照中观察到异常FHIT mRNA转录。1/16(6%)细胞系和7/55(13%)肿瘤不表达任何FHIT mRNA。cDNA测序显示外显子缺失,小DNA插入和两者的组合。基因组DNA分析表明,在两个髓系白血病细胞系的基因缺失。与所有正常类型的造血细胞相反,FHIT蛋白在8/18(44%)测试的肿瘤样品中明显减少或不存在。我们的数据表明,虽然异常FHIT mRNA转录被认为是在正常和恶性细胞,缺乏FHIT蛋白仅限于白血病。FHIT蛋白表达缺失可能与白血病的发生有关。
Alterations of the recently cloned fragile histidine triad (FHIT) gene at chromosome 3p14.2 are frequent in a variety of solid tumours and cancer cell lines. Based on these findings, FHIT has been proposed as a putative tumour-suppressor gene. We evaluated the mRNA expression of the FHIT gene in samples from 55 patients with various haematological malignancies (21 AML, 8 CML, 10 CLL, seven low-grade and nine high-grade Non-Hodgkin's lymphomas), in a panel of 16 leukaemia cell lines, in normal mature haematopoietic cells of both myeloid and lymphoid lineage, as well as in CD34+ haematopoietic progenitor cells. Aberrant FHIT mRNA transcripts were observed in 14/16 (88%) leukaemia cell lines, 43/55 (78%) primary haematological neoplasms, but also in 17/22 (77%) normal controls. 1/16 (6%) cell lines and 7/55 (13%) neoplasms did not express any FHIT mRNA. cDNA sequencing revealed exonic deletions, small DNA insertions and combinations of both. Analysis of genomic DNA showed gene deletions in two myeloid leukaemia cell lines. In contrast to all normal types of haematopoietic cells, FHIT protein was clearly reduced or absent in 8/18 (44%) neoplastic samples tested. Our data indicate that whilst aberrant FHIT mRNA transcripts are seen both in normal and malignant cells, lack of FHIT protein is restricted to leukaemia. Absent FHIT protein expression might contribute to leukaemogenesis.
DOI: 10.1021/bi961415t
发表时间: 1996-09-10
期刊: BIOCHEMISTRY
影响因子: 2.9
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DOI: --
发表时间: 1996
期刊: Cancer research.
影响因子: --
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