Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Hematology, ACUTE LYMPHOBLASTIC-LEUKEMIA, SECRETASE INHIBITOR PF-03084014, CHILDRENS ONCOLOGY GROUP, OF-FUNCTION MUTATIONS, CELL LEUKEMIA, TUMOR-SUPPRESSOR, ACTIVATING MUTATIONS, PATHWAY ACTIVATION, SIGNATURES DEFINE, CLONAL SELECTION, Humans, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine, Immunology, 3101 Biochemistry and cell biology, 3201 Cardiovascular medicine and haematology, 3213 Paediatrics

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. Since 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 on T-ALL pathogenesis, on the opportunities for the introduction of targeted therapy and on the challenges that are still ahead.