Blood Res 2017; 52(1):
Published online March 27, 2017
https://doi.org/10.5045/br.2017.52.1.55
© The Korean Society of Hematology
1Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India.
2Department of Hematology and Immunology, Cancer Institute (WIA), Chennai, India.
3Department of Biotechnology, Dr. M.G.R. Educational & Research Institute, Chennai, India.
Correspondence to : Natarajan Sudhakar, Ph.D. Department of Biotechnology, Dr. M.G.R. Educational and Research Institute (University), Maduravoyal, Chennai 600 095, India. nsudha79@gmail.com
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.
Keywords Immunoglobulin heavy(IGH), V-D-J, Precursor B-ALL, Gene rearrangements
Blood Res 2017; 52(1): 55-61
Published online March 27, 2017 https://doi.org/10.5045/br.2017.52.1.55
Copyright © The Korean Society of Hematology.
Natarajan Sudhakar1,3*, Thangarajan Rajkumar1, Kamalalayam Raghavan Rajalekshmy2, and Nirmala Karunakaran Nancy1
1Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India.
2Department of Hematology and Immunology, Cancer Institute (WIA), Chennai, India.
3Department of Biotechnology, Dr. M.G.R. Educational & Research Institute, Chennai, India.
Correspondence to: Natarajan Sudhakar, Ph.D. Department of Biotechnology, Dr. M.G.R. Educational and Research Institute (University), Maduravoyal, Chennai 600 095, India. nsudha79@gmail.com
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.
Keywords: Immunoglobulin heavy(IGH), V-D-J, Precursor B-ALL, Gene rearrangements
Frequency of IGHV gene subgroups in IGH gene rearrangements in precursor B-ALL.
Heteroduplex analysis of IGH gene rearrangements in precursor-B-ALL.
Table 1 . Clinical features of IGH gene rearrangements in children and adolescents and young adults (AYA)..
Table 2 . Frequency of IGH gene rearrangements in precursor B-ALL..
Table 3 . Clonal IGH rearranged sequences in precursor B-ALL..
Frequency of IGHV gene subgroups in IGH gene rearrangements in precursor B-ALL.
|@|~(^,^)~|@|Heteroduplex analysis of IGH gene rearrangements in precursor-B-ALL.