Breakpoint sites disclose the role of the V(D)J recombination machinery in the formation of T-cell receptor (TCR) and non-TCR associated aberrations in T-cell acute lymphoblastic leukemia

• Published in: Haematologica (Roma) 2013-08, Vol.98 (8), p.1173-1184
• Main Authors: Larmonie, Nicole S D, Dik, Willem A, Meijerink, Jules P P, Homminga, Irene, van Dongen, Jacques J M, Langerak, Anton W
• Format: Article
• Language: English
• Subjects: Animals; Chromosome Breakpoints; Humans; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Receptors, Antigen, T-Cell - genetics; Review; V(D)J Recombination - genetics
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2012.082156

Aberrant recombination between T-cell receptor genes and oncogenes gives rise to chromosomal translocations that are genetic hallmarks in several subsets of human T-cell acute lymphoblastic leukemias. The V(D)J recombination machinery has been shown to play a role in the formation of these T-cell receptor translocations. Other, non-T-cell receptor chromosomal aberrations, such as SIL-TAL1 deletions, have likewise been recognized as V(D)J recombination associated aberrations. Despite the postulated role of V(D)J recombination, the extent of the V(D)J recombination machinery involvement in the formation of T-cell receptor and non-T-cell receptor aberrations in T-cell acute lymphoblastic leukemia is still poorly understood. We performed a comprehensive in silico and ex vivo evaluation of 117 breakpoint sites from 22 different T-cell receptor translocation partners as well as 118 breakpoint sites from non-T-cell receptor chromosomal aberrations. Based on this extensive set of breakpoint data, we provide a comprehensive overview of T-cell receptor and oncogene involvement in T-ALL. Moreover, we assessed the role of the V(D)J recombination machinery in the formation of chromosomal aberrations, and propose an up-dated mechanistic classification on how the V(D)J recombination machinery contributes to the formation of T-cell receptor and non-T-cell receptor aberrations in human T-cell acute lymphoblastic leukemia.