T-Cell Receptor Gamma and Delta Gene Rearrangements and Junctional Region Characteristics in South Indian Patients With T-Cell Acute Lymphoblastic Leukemia

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Abstract

Clonal T-cell receptor (TCR) gamma and delta gene rearrangements were studied in 40 T-ALL cases (pediatrics, 29; adults, 11) using PCR with homo-heteroduplex analysis. At least one clonal TCRG or TCRD rearrangement was detected in 34 (85%) cases. TCR gamma (TCRG) rearrangement was detected in 25 (62.5%) cases that included 16 (55%) pediatrics and 9 (81.8%) adults. TCR delta (TCRD) rearrangement was detected in 14/40 (35%) cases, which included 12 (41%) pediatrics and 2 (18%) adults. The frequency of VγI-Jγ1.3/2.3 was significantly more in adults than pediatrics (81.8% vs. 41.3%,P= 0.02). InTCRD, Vδ1-Jδ1 was rearranged in 10 (25%) cases. The surface membrane CD3 positive cases are significantly associated with absence of TCRD rearrangements (surface membrane CD3+ TCRδ- 84% vs. surface membrane CD3- TCRδ- 48%,Pvalue = 0.03). Junctional region sequence analyzed with 10 cases each, ofTCRGandTCRD, revealed an average junctional region of 7.4 nucleotides (range 2-18 nucleotides) inTCRGand 27 nucleotides (range 14-42 nucleotides) inTCRD-complete rearrangements. InTCRG, trimming at the ends of Vγ and Jγ germline nucleotides resulted in deletion, on an average of 9.2 nucleotides. InTCRD, deletion of nucleotides of the Vδ and Jδ gene segments on an average was 3.5 nucleotides. The junctional region ofTCRDis more diverse thanTCRG; nevertheless, the frequency ofTCRGwas more than that ofTCRDand hence we rely more onTCRGclonal markers to quantitate the minimal residual disease in T-ALL.

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