Characterization of clonal immunoglobulin heavy (IGH) V-D-J gene rearrangements and the complementarity-determining region in South Indian patients with precursor B-cell acute lymphoblastic leukemia

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating gastro-entero pancreatic neuro endocrine tumours

The objective of this study was to evaluate the performance and utility of 99mTc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors [GPNETs]. 22 patients [median age, 46 years] with histologically proven gastroentero-pancreatic NETs underwent 99mTc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq [10-15 mCi] of 99mTc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively [tumor to tumor to normal liver ratios on SPECT -CT images]. Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with 99mTc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. 99mTc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor [P<0.001] and metastases [P<0.0001]. It changed the management strategy in 6 patients [31.8%] and supported management decisions in 8 patients [36.3%].99mTc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options

Diversity of T-cell receptor gene rearrangements in South Indian patients with common Acute Lymphoblastic Leukemia

Precursor B-Acute Lymphoblastic Leukemia [precursor B-ALL] occurs due to the uncontrolled proliferation of B-lymphoid precursors arrested at a particular stage of B-cell development. Precursor-B-ALL is classified mainly into pro-B-ALL, common-ALL and pre-B-ALL. The Common Acute Lymphoblastic Antigen CD10 is the marker for common-ALL. This study was aimed to examine the diversity of T-cell receptor Gamma [TCRG] and T-cell receptor Delta [TCRD] gene rearrangements in South Indian Common-ALL patients. Clonality of TCRG and TCRD was studied in 52 cases [pediatric=41 and adolescents and young adults=11] of common-ALL. TCRG and TCRD gene rearrangements were amplified by PCR and the clonality was assessed by Heteroduplex analysis of amplified products. In pediatric common-ALL, clonal TCRG and TCRD gene rearrangements were detected in 19 [46.3%] and 18 [43.9%] cases respectively. In adolescents and young adults [AYA], TCRG was rearranged in 8 [72.7%] cases and TCRD was rearranged in 4 [36.3%] cases. In the present study of common-ALL, the frequency of a TCRG rearrangement V gamma II-J gamma 1.3/2.3 was significantly high in AYA compared to pediatric [36.3% vs 4.8%; p<0.025]. Thus, V gamma II-J gamma 1.3/2.3 was highly diverse in AYA compared to pediatric. That shows the difference in biology of the disease between pediatric and AYA in South Indian population. The reason for the high frequency of V gamma II-J gamma 1.3/2.3 in AYA of common-ALL in South Indian population in connection with unknown infectious agents or environmental carcinogens needs to be evaluated further