Galligan Leeona, Catherwood Mark A, Matthews Christine, Morris T C M 'Curly', Alexander H Dennis
Hemato-Oncology Laboratory, Department of Hematology, Belfast City Hospital, Belfast, United Kingdom.
Leuk Lymphoma. 2008 Apr;49(4):763-8. doi: 10.1080/10428190801911696.
Biased IgHV gene usage in chronic lymphocytic leukemia (CLL) is well documented and suggests antigen involvement in leukemogenesis. IgHV1-69 is one of the most frequently rearranged IgHV genes in CLL and the majority of IgHV1-69 cases lack somatic hypermutation and display poor prognosis. However, its independent prognostic impact remains uncertain given reports showing a low proportion of mutated IgHV1-69 cases and stereotyped IgHV1-69 subsets with divergent clinical outcome. We assessed the frequency and clinical significance of IgHV1-69 gene usage in a cohort of 330 CLL patients. Functional IgHV1-69 gene rearrangements were detected in 32 cases (9.7%), 31 of which were characterised further. Seven (22.6%) were found to have undergone somatic hypermutation. This subgroup had shorter and more diverse complementarity determining region 3 (CDR3) sequences compared with unmutated IgHV1-69 cases. In addition, mutated IgHV1-69 gene status was associated with lower cell surface CD38 expression and less progressive disease as monitored by Binet staging, lymphocyte doubling time and requirement of chemotherapeutic intervention. To conclude, we present data confirming that IgHV1-69 gene rearrangements in CLL are not exclusively associated with unmutated IgHV status. In addition, we show that a somatically hypermutated subgroup may demonstrate more indolent characteristics despite the general association of IgHV1-69 gene usage with aggressive disease.
慢性淋巴细胞白血病（CLL）中IgHV基因使用存在偏向性，这已得到充分证实，并提示抗原参与白血病发生过程。IgHV1-69是CLL中最常发生重排的IgHV基因之一，大多数IgHV1-69病例缺乏体细胞超突变，且预后较差。然而，鉴于有报道显示IgHV1-69突变病例比例较低以及具有不同临床结局的定型IgHV1-69亚群，其独立的预后影响仍不确定。我们评估了330例CLL患者队列中IgHV1-69基因使用的频率及临床意义。在32例（9.7%）患者中检测到功能性IgHV1-69基因重排，其中31例进一步进行了特征分析。发现7例（22.6%）发生了体细胞超突变。与未突变的IgHV1-69病例相比，该亚组的互补决定区3（CDR3）序列更短且更多样化。此外，通过Binet分期、淋巴细胞倍增时间和化疗干预需求监测发现，IgHV1-69基因突变状态与较低的细胞表面CD38表达及较少的疾病进展相关。总之，我们提供的数据证实CLL中的IgHV1-69基因重排并非仅与未突变的IgHV状态相关。此外，我们表明，尽管IgHV1-69基因使用通常与侵袭性疾病相关，但体细胞超突变亚组可能表现出更惰性的特征。
