Abstract: Objective To investigate the characteristics of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement patterns in childhood T-cell acute lymphoblastic leukemia(T-ALL), and its correlation with the clinical and biological characteristics of the patients.Methods The study included 52 newly diagnosed pediatric T-ALL patients enrolled at Beijing Children's Hospital from January 1st, 2005 to December 31th, 2008. Analyze the Ig/TCR gene rearrangement of bone marrow mononuclear cells at diagnosis, including the incidence of TCRB, TCRG, TCRD and IgH gene rearrangements and types, germline fragment usage and junctional characteristics.According to the rearrangement of each gene, it was divided into positive and negative groups, and then the clinical and biological characteristics were compared between different groups.Results ① There were 37 males(71.2%) among the 52 children,aged from 1.8 to 16 years , with a median of 8 years,and the median WBC was 140.5 (2.7-667.1) ×10⁹·L^-1. There were 38 cases of IR(73.1%), and 14 cases of HR(26.9%). The follow-up time was 1.2 to 171.7 months and the median follow-up time was 136.3 months. There were 38 cases(73.1%) of long-term complete remission, 10 cases(19.2%) of recurrence and 4 cases(7.7%) of death from other cases. ②The incidence of TCRB, TCRG, TCRD and IgH clonal gene rearrangement was 85%, 85%, 38% and 21%, respectively. Ninety-four percent of the children were detected at least one gene rearrangement, and 88% of the children were at least examined two gene rearrangements. The TCRB, TCRD, TCRG, and IgH rearrangements were dominated by complete V_β-(D_β)-J_β, V_δ-J_δ, V_γI-J_γ1.3/2.3, and D_H-J_H incomplete rearrangement, respectively. Different combinations of germline gene segments resulted in the combinatorial diversity, and the deletion and random insertion of nucleotides at the junction sites created an enormous junctional diversity. ③Among the ten relapsed children, six were compared the Ig/TCR gene rearrangement pattern between diagnosis and recurrence,and four patients had recurrence of Ig/TCR gene rearrangement pattern at the time of initial diagnosis and two patients changed. ④The positive rates of SIL-TAL1 fusion gene were 0 in 11 patients with positive IgH rearrangement and 34.1% (14/41) in 41 children with negative IgH rearrangement,P=0.025 . ⑤The high-risk ratio of TCRB gene rearrangement positive group (20.5%, 9/44) was lower than that of negative group (62.5%, 5/8), P=0.025. The remission rate at the 33rd day of the TCRB or TCRG gene rearrangement positive group (89.4%, 42/44) was higher than that of the negative group (10.6%, 5/8), P=0.022, and the ratio of MRD level ≥10^-3 on the 78th day (10.8%, 4/37) was lower than the negative group (50.0%, 3/6), P=0.045.Conclusion The usage of germline fragments of clonal Ig/TCR gene rearrangements and the DNA sequence of their junction regions were diverse, which was helpful for further screening of MRD markers of T-ALL in children.

Key words: Childhood T-cell acute lymphoblastic leukemia, Gene rearrangement, Immunoglobulin, T cell receptor