Department of Hematopathology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
Int J Cancer. 2011 Jun 1;128(11):2759-64. doi: 10.1002/ijc.25605. Epub 2010 Oct 26.
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 using IGHV4-39; light chain analysis revealed identical IGKV1-39 use. 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.
t(14;19)(q32;q13)是一种在多种 B 细胞白血病和淋巴瘤中报道的反复出现的染色体易位，包括慢性淋巴细胞白血病（CLL）。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情况。所有病例均未发生突变，并且 10 例 IGHV 基因与种系序列最小偏差。在 11 例患者中的 7 例中，我们使用 IGHV4-39 发现了同源重链重排；轻链分析显示 IGKV1-39 的使用相同。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 CDR3）基因的显著定型性。这些发现提出了这样一种可能性，即特定抗原驱动可能参与了 t(14;19)(q32;q13)阳性 CLL 细胞的克隆发展和/或选择。我们的发现支持这样一种假设，即通过特定抗原受体的刺激信号可能促进 CLL 前体细胞或携带独特染色体异常的 CLL 克隆的扩增。
