Novel insights into the mechanism of t(14;18)(q32;q21) translocation in follicular lymphoma

Leukemia & Lymphoma
B NadelU Jäger

Abstract

The t(14:18)(q32:q21) chromosomal translocation and the ensuing overexpression of the BCL-2 proto-oncogene are strongly associated with the pathogenesis of follicular lymphoma. At the molecular level, the translocation process arises from the illegitimate rearrangement between the BCL-2 proto-oncogene and the immunoglobulin heavy chain (IgH) locus. Due to the presence of the D(H) and J(H) gene segments from the IgH locus as well as de novo nucleotide additions at the breakpoints, the translocation process has been assumed to result from a mistake occurring during V(D)J recombination in early B-cells in the bone marrow. However, recent detailed molecular analyses of both the direct and reciprocal breakpoints have revealed that the t(14;18) translocation is a more complex process than previously thought, and have challenged this traditional view. Here we review these observations, and discuss the intriguing possibility that t(14;18) translocation could preferentially occur in the germinal centers during receptor revision, and involves both V(D)J recombination and somatic hypermutation mechanisms.

Citations

Jan 10, 2002·The Journal of Experimental Medicine·Rodrig MarculescuBertrand Nadel
Nov 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Joseph L WiemelsSharon R Pine
Jun 29, 2005·Virchows Archiv : an International Journal of Pathology·Jean-Louis DargentChristiane De Wolf-Peeters
Dec 7, 2007·International Journal of Hematology·Ponlapat RojnuckarinTanin Intragumtornchai
Aug 23, 2008·Biochimica Et Biophysica Acta·Mridula NambiarSathees C Raghavan
Jul 9, 2003·Immunological Reviews·Kevin D MillsFrederick W Alt
Dec 2, 2010·Blood·Sietse M AukemaPhilip M Kluin
Mar 25, 2017·Molecular Medicine Reports·Venerando RapisardaCarla Loreto

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