title: The genetics and molecular biology of T-ALL.
abstract: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy caused by the accumulation of genomic lesions that affect the development of T cells. For many years, it has been established that deregulated expression of transcription factors, impairment of the CDKN2A/2B cell-cycle regulators, and hyperactive NOTCH1 signaling play prominent roles in the pathogenesis of this leukemia. In the past decade, systematic screening of T-ALL genomes by high-resolution copy-number arrays and next-generation sequencing technologies has revealed that T-cell progenitors accumulate additional mutations affecting JAK/STAT signaling, protein translation, and epigenetic control, providing novel attractive targets for therapy. In this review, we provide an update on our knowledge of T-ALL pathogenesis, the opportunities for the introduction of targeted therapy, and the challenges that are still ahead.
authors.affiliation: Department of Oncology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.|Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Tiziana
authors.identifier: 0000-0002-1344-8459
authors.initials: T
authors.lastname: Girardi
authors.affiliation: Leuven Cancer Institute, Leuven, Belgium.|Center for Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB) Leuven, Belgium; and.|Center for Human Genetics, KU Leuven, Leuven, Belgium.
authors.forename: Carmen
authors.initials: C
authors.lastname: Vicente
authors.affiliation: Leuven Cancer Institute, Leuven, Belgium.|Center for Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB) Leuven, Belgium; and.|Center for Human Genetics, KU Leuven, Leuven, Belgium.
authors.forename: Jan
authors.identifier: 0000-0001-6626-5843
authors.initials: J
authors.lastname: Cools
authors.affiliation: Department of Oncology, Katholieke Universiteit (KU) Leuven, Leuven, Belgium.|Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Kim
authors.identifier: 0000-0002-7420-9531
authors.initials: K
authors.lastname: De Keersmaecker
mesh_terms: D006801:Humans; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*