title: Advances in the molecular pathobiology of B-lymphoblastic leukemia.
abstract: B-lymphoblastic leukemia/lymphoma, also known as B-acute lymphoblastic leukemia, is derived from B-cell progenitors. B-acute lymphoblastic leukemia occurs predominantly in children, but can occur at any age. Risk-adapted intensive chemotherapy is effective in treating most children with B-acute lymphoblastic leukemia, but this approach is less successful in adults. Recent developments in genome-wide genetic analysis in B-acute lymphoblastic leukemia have provided insights into disease pathogenesis and prognosis. B-acute lymphoblastic leukemia cases usually carry a primary genetic event, often a chromosome translocation, and a constellation of secondary genetic alterations that are acquired and selected dynamically in a nonlinear fashion. These genetic changes commonly affect cellular mechanisms that control B-cell differentiation and proliferation. The cooperative interaction between inactivation of hematopoietic transcription factors involved in differentiation (class II mutation) and activating mutations involved in cell proliferation (class I mutation) is reminiscent of the pathogenic model of acute myeloid leukemia. The resulting improved molecular understanding of B-acute lymphoblastic leukemia is helping to refine disease risk stratification and discover new therapeutic approaches for patients with refractory disease. In this review, we first summarize the clinicopathologic and immunophenotypic features of B-acute lymphoblastic leukemia and introduce current understanding of B-cell development and B-acute lymphoblastic leukemia leukemogenesis. We then focus on recent advances in genetic analysis and gene expression profiling of B-acute lymphoblastic leukemia and discuss the implications of these findings for disease evolution, risk prediction, and possible novel therapeutic approaches.
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. yzhou7@mdanderson.org
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: M James
authors.initials: MJ
authors.lastname: You
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: Gary
authors.initials: G
authors.lastname: Lu
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002648:Child; D020869:Gene Expression Profiling; D006801:Humans; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology