title: Molecular basis and clinical significance of genetic aberrations in B-cell precursor acute lymphoblastic leukemia.
abstract: B-Cell precursor acute lymphoblastic leukemia (BCP-ALL) arises from recurrent genetic insults that block precursor B-cell differentiation and drive aberrant proliferation and cell survival. Risk-adapted intensive chemotherapy is effective in curing the majority of children with BCP-ALL (>85%), but some children, not considered "high risk" and treated accordingly, experience a hematologic relapse. Moreover, survival rates in adults are significantly lower (∼40%) than those in children. Recent developments in genomewide genetic analysis have provided a wide range of chromosomal and genomic abnormalities characterizing BCP-ALL, several of which are associated with patient outcome. These findings provide an opportunity to adapt risk stratification and treatment schedules and to identify new druggable targets. In this review, we discuss the established and novel genetic alterations in BCP-ALL, their molecular background, and their potential use in risk stratification and treatment of BCP-ALL.
authors.affiliation: Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Ghazavi
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, Ghent University Hospital, Ghent, Belgium.
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
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: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Vlierberghe
authors.affiliation: Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium. Electronic address: Barbara.DeMoerloose@uzgent.be.
authors.forename: Barbara
authors.initials: B
authors.lastname: De Moerloose
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018570:Risk Assessment
chemical_list: D016044:Fusion Proteins, bcr-abl