LYMPHOMA-ASSOCIATED TRANSLOCATION T(14-18) IN BLOOD B-CELLS OF NORMAL INDIVIDUALS
LYMPHOMA-ASSOCIATED TRANSLOCATION T(14-18) IN BLOOD B-CELLS OF NORMAL INDIVIDUALS
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DOI：
10.1182/blood.v85.9.2528.bloodjournal8592528
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发表时间：
1995-05-01
期刊：
影响因子：
20.3
通讯作者：
KLUIN, PM
中科院分区：
文献类型：
--
作者：
LIMPENS, J;STAD, R;KLUIN, PM
连续的致癌步骤是产生癌症所必需的，在许多B细胞淋巴瘤中，染色体易位被认为是早期致癌的打击。我们研究了是否淋巴瘤相关的t（14;18）涉及BCL 2癌基因可以发生在恶性肿瘤的背景之外，为此，我们通过非常敏感的套式聚合酶链反应（PCR）广泛筛选来自健康献血者的血细胞，寻找14 q32上JH 1 -5的断点连接和18 q21上BCL 2的主要断点区域。在每个个体中，单核细胞，粒细胞。在5 - 7个独立进行的PCR中分别测试少量分选的B细胞和T细胞（总共，每个个体每个级分0.5 × 10（5）至1.0 × 10（6）个细胞）。扩增产物与内部BCL 2探针和JH探针杂交后进行测序。9例个体中有6例具有t（14;18）断点，易位仅限于B细胞，估计频率为1/10（5）或更低的循环B细胞。总之，51次B细胞实验中有23次为阳性，而48次T细胞实验中有1次为阳性，47次粒细胞实验中有2次为阳性。与单核细胞组分中存在4.7%至13.0% B细胞一致，这些组分中只有极少数（47次中的4次）检测为阳性，序列分析表明，6例患者中有4例携带2 ~ 5个不相关的t（14;18）细胞克隆，所有断点的结构与滤泡性淋巴瘤相似。我们认为，正常个体中有规律地产生具有ttl 4; 18）易位的B细胞，但只有极少数具有该易位的细胞会获得额外的致癌命中，而这些额外的致癌命中是建立恶性表型所必需的。(C)1995年，美国血液学会。
Successive oncogenic steps are necessary to generate cancer, In many B-cell lymphomas, chromosomal translocations are considered to be an early oncogenic hit. We investigated whether the lymphoma-associated t(14;18) involving the BCL2 oncogene can occur outside the context of malignancy, To this end, we extensively screened blood cells from healthy blood donors by a very sensitive seminested polymerase chain reaction (PCR) for breakpoint junctions at JH1-5 on 14q32 and the major breakpoint region of BCL2 on 18q21. In each individual, mononuclear cells, granulocytes. few-sorted B cells, and T cells were separately tested in five to seven independently performed PCRs (in total, 0.5 x 10(5) to 1.0 x 10(6) cells per fraction per individual). Amplification products that hybridized with an internal BCL2 probe and a JH probe were sequenced. Six of nine individuals harbored t(14;18) breakpoints, Translocations were restricted to B cells, with an estimated frequency of 1 in 10(5) or less circulating B cells. In total, 23 of 51 experiments on B cells were positive in contrast to 1 of 48 on T cells and 2 of 47 experiments on granulocytes, Consistent with the presence of 4.7% to 13.0% B cells in the mononuclear cell fractions, only very few (4 of 47) tests were positive in these fractions, Sequence analysis showed that four of six individuals harbored two to five unrelated t(l4;18)-carrying B-cell clones, All breakpoints had a structure similar to that in follicular lymphoma. We propose that B cells with the ttl 4; 18) translocation are regularly generated in normal individuals, but that only very few cells with the translocation will acquire the additional oncogenic hits necessary to establish the malignant phenotype. (C) 1995 by The American Society of Hematology.