The B cell antigen receptor in atypical chronic lymphocytic leukemia with t(14;19)(q32;q13) demonstrates remarkable stereotypy.
The B cell antigen receptor in atypical chronic lymphocytic leukemia with t(14;19)(q32;q13) demonstrates remarkable stereotypy.
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t(14;19)(q32;q13) 的非典型慢性淋巴细胞白血病中的 B 细胞抗原受体表现出显着的刻板性。
DOI：
10.1002/ijc.25605
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发表时间：
2011
影响因子：
6.4
通讯作者：
Abruzzo,LynneV
中科院分区：
文献类型：
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作者：
Schweighofer,CarmenD;Huh,YangO;Luthra,Rajyalakshmi;Sargent,RachelL;Ketterling,RhettP;Knudson,RyanA;Barron,LynnL;Medeiros,LJeffrey;Keating,MichaelJ;Abruzzo,LynneV
t（14; 19）（q32; q13）是一种在多种B细胞白血病和淋巴瘤（包括慢性淋巴细胞白血病（CLL））中报告的复发性染色体易位。与t（14;19）相关的CLL病例通常具有非典型的形态学和免疫表型特征以及未突变的免疫球蛋白重链（IGH）可变区（V）基因，与侵袭性临床病程相关。我们分析了11例t（14;19）阳性CLL患者的IGHV体细胞突变状态和基因使用。所有病例均未发生突变，10例IGHV基因与种系序列的偏差最小。在11例患者中的7例中，我们发现使用IGHV 4 - 39的同源重链重排;轻链分析显示使用相同的IGKV 1 - 39。相应的V-（D）-J序列显示免疫球蛋白重链和κ轻链互补决定区3（H/K CDR 3）基因的显著定型。这些发现提高了特异性抗原驱动参与t（14;19）（q32;q13）阳性CLL细胞的克隆发育和/或选择的可能性。我们的研究结果支持这一假设，即通过特异性抗原受体的刺激信号可能促进CLL前体细胞或CLL克隆的扩增，这些克隆具有明显的染色体异常。
The t(14;19)(q32;q13) is a recurrent chromosomal translocation reported in a variety of B‐cell leukemias and lymphomas, including chronic lymphocytic leukemia (CLL). CLL cases associated with t(14;19) often have atypical morphologic and immunophenotypic features and unmutated immunoglobulin heavy chain (IGH) variable region (V) genes, associated with an aggressive clinical course. We analyzed IGHV somatic mutation status and gene use in 11 patients with t(14;19)‐positive CLL. All cases were unmutated, and the IGHV genes in 10 cases showed minimal deviation from germline sequences. In 7 of 11 patients, we found homologous heavy chain rearrangements usingIGHV4‐39; light chain analysis revealed identicalIGKV1‐39use. Corresponding V‐(D)‐J sequences demonstrated remarkable stereotypy of the immunoglobulin heavy and kappa light chain complementarity determining region 3 (H/K CDR3) genes. These findings raise the possibility that specific antigen drive is involved in the clonal development and/or selection of t(14;19)(q32;q13)‐positive CLL cells. Our findings support the hypothesis that stimulatory signals through specific antigen receptors may promote the expansion of either CLL precursor cells or CLL clones that harbor distinct chromosomal abnormalities.