Sudhakar Natarajan, Rajkumar Thangarajan, Rajalekshmy Kamalalayam Raghavan, Nancy Nirmala Karunakaran
Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India.; Department of Biotechnology, Dr. M.G.R. Educational & Research Institute, Chennai, India.
Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India.
Blood Res. 2017 Mar;52(1):55-61. doi: 10.5045/br.2017.52.1.55. Epub 2017 Mar 27.
This study characterized clonal IG heavy V-D-J (IGH) gene rearrangements in South Indian patients with precursor B-cell acute lymphoblastic leukemia (precursor B-ALL) and identified age-related predominance in VDJ rearrangements.
IGH rearrangements were studied in 50 precursor B-ALL cases (common ALL=37, pre-B ALL=10, pro-B ALL=3) by polymerase chain reaction (PCR) heteroduplex analysis. Twenty randomly selected clonal IGH rearrangement sequences were analyzed using the IMGT/V-QUEST tool.
Clonal IGH rearrangements were detected in 41 (82%) precursor B-ALL cases. Among the IGHV1-IGHV7 subgroups, IGHV3 was used in 25 (50%) cases. Among the IGHD1-IGHD7 genes, IGHD2 and IGHD3 were used in 8 (40%) and 5 (25%) clones, respectively. Among the IGHJ1-IGHJ6 genes, IGHJ6 and IGHJ4 were used in 9 (45%) and 6 (30%) clones, respectively. In 6 out of 20 (30%) IGH rearranged sequences, CDR3 was in frame whereas 14 (70%) had rearranged sequences and CDR3 was out of frame. A somatic mutation in Vmut/Dmut/Jmut was detected in 14 of 20 IGH sequences. On average, Vmut/Dmut/Jmut were detected in 0.1 nt, 1.1 nt, and 0.2 nt, respectively.
The IGHV3 gene was frequently used whereas lower frequencies of IGHV5 and IGHV6 and a higher frequency of IGHV4 were detected in children compared with young adults. The IGHD2 and IGHD3 genes were over-represented, and the IGHJ6 gene was predominantly used in precursor-B-ALL. However, the IGH gene rearrangements in precursor-B-ALL did not show any significant age-associated genotype pattern attributed to our population.
本研究对南印度前体B细胞急性淋巴细胞白血病（前体B-ALL）患者的克隆性免疫球蛋白重链V-D-J（IGH）基因重排进行了特征分析，并确定了VDJ重排在年龄上的优势。
采用聚合酶链反应（PCR）异源双链分析对50例前体B-ALL病例（普通ALL = 37例，前B-ALL = 10例，前体B-ALL = 3例）进行IGH重排研究。使用IMGT/V-QUEST工具对20个随机选择的克隆性IGH重排序列进行分析。
在41例（82%）前体B-ALL病例中检测到克隆性IGH重排。在IGHV1-IGHV7亚组中，25例（50%）病例使用了IGHV3。在IGHD1-IGHD7基因中，分别有8个（40%）和5个（25%）克隆使用了IGHD2和IGHD3。在IGHJ1-IGHJ6基因中，分别有9个（45%）和6个（30%）克隆使用了IGHJ6和IGHJ4。在20个IGH重排序列中的6个（30%）中，互补决定区3（CDR3）读框内，而14个（70%）重排序列的CDR3读框外。在20个IGH序列中的14个检测到Vmut/Dmut/Jmut中的体细胞突变。平均而言，分别在0.1个核苷酸、1.1个核苷酸和0.2个核苷酸中检测到Vmut/Dmut/Jmut。
与年轻成年人相比，儿童中IGHV3基因使用频繁，而IGHV5和IGHV6频率较低，IGHV4频率较高。IGHD2和IGHD3基因过度表达，IGHJ6基因在前体B-ALL中占主导地位。然而，前体B-ALL中的IGH基因重排在我们的人群中未显示出任何与年龄相关的显著基因型模式。
