P53 mutation in acute T cell lymphoblastic leukemia is of somatic origin and is stable during establishment of T cell acute lymphoblastic leukemia cell lines.
P53 mutation in acute T cell lymphoblastic leukemia is of somatic origin and is stable during establishment of T cell acute lymphoblastic leukemia cell lines.
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急性T细胞急性淋巴细胞白血病中的P53突变是体细胞起源的，并且在T细胞急性淋巴细胞白血病细胞系的建立过程中是稳定的。
DOI：
10.1172/jci116435
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Haas,M
中科院分区：
文献类型：
--
作者：
Yeargin,J;Cheng,J;Yu,AL;Gjerset,R;Bogart,M;Haas,M
对T细胞急性淋巴细胞白血病（T-ALL）患者捐献的样本进行p53肿瘤抑制基因突变筛查。T-ALL复发患者H.A.发现在p53基因的密码子175处具有杂合点突变。为了确定这是否是遗传突变，建立了B细胞系（HABL）。白血病T细胞系（HATL）的同时建立的生长外周血白血病T细胞在低氧张力的培养基中补充IGF-I。以前我们已经表明> 60%的白血病T细胞系在p53基因中具有突变（Cheng，J.，和M.哈斯1990.摩尔Cell. 10：5502），可能起源于供体的白血病细胞的突变，或可能在细胞系建立期间诱导的突变。为了回答HATL系的建立是否与p53突变的诱导相关，对HATL和HABL系的cDNA进行测序。HATL系保留了患者白血病细胞中存在的相同杂合p53突变。HABL系缺乏p53突变。特异性抗p53抗体的免疫沉淀显示，HATL细胞产生突变型和野生型免疫表型的p53蛋白，而HABL系仅合成野生型p53蛋白。HATL细胞具有异常核型，而HABL细胞具有正常的二倍体核型。这些实验表明：（a）复发T-ALL患者HA的白血病细胞中发生了p53突变;（B）突变是体细胞而不是遗传起源;（c）突变与白血病相关;（d）人白血病细胞系的建立不需要与p53突变的体外诱导相关。可能重要的是，患者HA属于复发性T-ALL患者的一个类别，其中不能诱导第二次缓解。
Samples donated by patients with T cell acute lymphoblastic leukemia (T-ALL) were screened for mutations of the p53 tumor suppressor gene. Peripheral blood cells of T-ALL relapse patient H.A. were found to possess a heterozygous point mutation at codon 175 of the p53 gene. To determine whether this was an inherited mutation, a B cell line (HABL) was established. Leukemic T cell lines (HATL) were concurrently established by growing peripheral blood leukemic T cells at low oxygen tension in medium supplemented with IGF-I. Previously we had shown that > 60% of leukemic T cell lines possessed mutations in the p53 gene (Cheng, J., and M. Hass. 1990. Mol. Cell. Biol. 10:5502), mutations that might have originated with the donor's leukemic cells, or might have been induced during establishment of the cell lines. To answer whether establishment of the HATL lines was associated with the induction of p53 mutations, cDNAs of the HATL and HABL lines were sequenced. The HATL lines retained the same heterozygous p53 mutation that was present in the patient's leukemic cells. The HABL line lacked p53 mutations. Immunoprecipitation with specific anti-p53 antibodies showed that HATL cells produced p53 proteins of mutant and wild type immunophenotype, while the HABL line synthesized only wild-type p53 protein. The HATL cells had an abnormal karyotype, while the HABL cells possessed a normal diploid karyotype. These experiments suggest that (a) p53 mutation occurred in the leukemic cells of relapse T-ALL patient HA; (b) the mutation was of somatic rather than hereditary origin; (c) the mutation was leukemia associated; and (d) establishment of human leukemia cell lines needs not be associated with in vitro induction of p53 mutations. It may be significant that patient HA belonged to a category of relapse T-ALL patients in whom a second remission could not be induced.Images