title: Novel biological insights in T-cell acute lymphoblastic leukemia.
abstract: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer that accounts for about 15% of pediatric and 25% of adult acute lymphoblastic leukemia (ALL) cases. It is considered as a paradigm for the multistep nature of cancer initiation and progression. Genetic and epigenetic reprogramming events, which transform T-cell precursors into malignant T-ALL lymphoblasts, have been extensively characterized over the past decade. Despite our comprehensive understanding of the genomic landscape of human T-ALL, leukemia patients are still treated by high-dose multiagent chemotherapy, potentially followed by hematopoietic stem cell transplantation. Even with such aggressive treatment regimens, which are often associated with considerable acute and long-term side effects, about 15% of pediatric and 40% of adult T-ALL patients still relapse, owing to acquired therapy resistance, and present with very dismal survival perspectives. Unfortunately, the molecular mechanisms by which residual T-ALL tumor cells survive chemotherapy and act as a reservoir for leukemic progression and hematologic relapse remain poorly understood. Nevertheless, it is expected that enhanced molecular understanding of T-ALL disease biology will ultimately facilitate a targeted therapy driven approach that can reduce chemotherapy-associated toxicities and improve survival of refractory T-ALL patients through personalized salvage therapy. In this review, we summarize recent biological insights into the molecular pathogenesis of T-ALL and speculate how the genetic landscape of T-ALL could trigger the development of novel therapeutic strategies for the treatment of human T-ALL.
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Kaat
authors.initials: K
authors.lastname: Durinck
authors.affiliation: Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Unit for Molecular Oncology, VIB Inflammation Research Center, Ghent, Belgium; Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Goossens
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Peirs
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Annelynn
authors.initials: A
authors.lastname: Wallaert
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Van Loocke
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Matthijssens
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium; Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Unit for Molecular Oncology, VIB Inflammation Research Center, Ghent, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Pieters
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Gloria
authors.initials: G
authors.lastname: Milani
authors.affiliation: Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Lammens
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Rondou
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.affiliation: Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: De Moerloose
authors.affiliation: Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.affiliation: Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
authors.forename: Jody
authors.initials: J
authors.lastname: Haigh
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium.
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.affiliation: Center for Medical Genetics, Department for Pediatrics, Ghent, Belgium. Electronic address: pieter.vanvlierberghe@ugent.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Vlierberghe
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D065150:Cellular Reprogramming; D002648:Child; D002675:Child, Preschool; D044127:Epigenesis, Genetic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D054504:Precursor Cells, T-Lymphoid / Q000378:metabolism / Q000473:pathology; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy