Molecular pathogenesis of T-cell leukaemia and lymphoma

Abstract

T-cell acute lymphoblastic leukaemia (T-ALL) is induced by the transformation of T-cell progenitors and mainly occurs in children and adolescents. Although treatment outcome in patients with T-ALL has improved in recent years, patients with relapsed disease continue to have a poor prognosis. It is therefore important to understand the molecular pathways that control both the induction of transformation and the treatment of relapsed disease. In this Review, we focus on the molecular mechanisms responsible for disease induction and maintenance. We also compare the physiological progression of T-cell differentiation with T-cell transformation, highlighting the close relationship between these two processes. Finally, we discuss potential new therapies that target oncogenic pathways in T-ALL.

Acetylation controls Notch3 stability and function in T-cell leukemia

“…Development and progression of T-ALL have been linked to mis-regulation of Notch signaling (Aifantis et al, 2008;Clappier et al, 2010). In particular, we previously showed that Notch3 intracellular domain (N3 IC ) transgenic (tg) mice develop a very aggressive T-ALL with high penetrance, representing a suitable model of the human disease (Bellavia et al, 2000).…”

It's T-ALL about Notch

“…However, certain aspects about T-ALL make it a more aggressive disease with a poorer clinical outcome than B-ALL. T-ALL patients have a higher percentage of induction failure, and rate of relapse and invasion into the central nervous system (reviewed in Aifantis et al, 2008). The challenge to acquiring 100% remission in T-ALL treatment is the subset of patients (20-25%) whose disease is refractory to initial treatments or relapses after a short remission period due to drug resistance.…”

Mécanisme d’action des oncogènes à homéodomaine TLX dans les LAL-T

“…L'oncogenèse des LAL-T est multigé-nique, avec coexistence de plusieurs dérégulations oncogéniques chez le même patient [4]. Parmi les sousgroupes identifiés, figure l'important groupe TLX marqué par la surexpression des oncogènes TLX1 ou TLX3.…”

“…Ea CAT [4]. Un métabolisme primitif nécessite égale-ment que ces polymères soient capables de se replier dans des structures tertiaires stables ayant des fonctionnalités élaborées telles que la reconnaissance d'un ligand et la catalyse [5].…”