ATM-deficient thymic lymphoma is associated with aberranttcrdrearrangement and gene amplification

Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development

“…The major consequence of immunodeficiency in A-T patients is an increased likelihood of developing infections, and this defect is a significant cause of death. Specifically, ATM deficiency or inactivation leads to increased genome instability and a highly elevated predisposition to lymphoid cancers due to aberrant translocations involving Tcra/Tcrd (Liyanage et al 2000;Bredemeyer et al 2006;Matei et al 2007;Vacchio et al 2007;Zha et al 2010;Isoda et al 2012). In fact, 10 % of all A-T patients develop a malignancy due to translocations and inversions involving chromosomes 7 and 14 at specific breakpoints at the Tcrb and Tcra/Tcrd loci, respectively.…”

“…One of the most important features of A-T is the increased predisposition for T-cell acute lymphoblastic leukemia (T-ALL) and prolymphocytic leukemia. In fact, almost all ATM À/À mice die due to thymic lymphomas derived from aberrant Tcrd translocations and incorrect repair of RAG-1/2-induced double-strand breaks (Liyanage et al 2000;Zha et al 2010;Isoda et al 2012). In addition to these problems, A-T patients also present neurologic defects resulting from cerebellar degeneration as well as abnormal eye movements, dysarthria, hypogonadism, and growth retardation.…”