title: Immunoglobulin heavy chain locus chromosomal translocations in B-cell precursor acute lymphoblastic leukemia: rare clinical curios or potent genetic drivers?
abstract: Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus define common subgroups of B-cell lymphoma but are rare in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Recent fluorescent in situ hybridization and molecular cloning studies have identified several novel IGH translocations involving genes that play important roles in normal hemopoiesis, including the cytokine receptor genes CRLF2 and EPOR, all members of the CCAAT enhancer-binding protein gene family, as well as genes not normally expressed in hemopoietic cells including inhibitor of DNA binding 4. IGH translocation results in deregulated target gene expression because of juxtaposition with IGH transcriptional enhancers. However, many genes targeted by IGH translocations are also more commonly deregulated in BCP-ALL as a consequence of other genetic or epigenetic mechanisms. For example, interstitial genomic deletions also result in deregulated CRLF2 expression, whereas EPOR expression is deregulated as a consequence of the ETV6-RUNX1 fusion. The possible clinical importance of many of the various IGH translocations in BCP-ALL remains to be determined from prospective studies, but CRLF2 expression is associated with a poor prognosis. Despite their rarity, IGH chromosomal translocations in BCP-ALL therefore define not only new mechanisms of B-cell transformation but also clinically important subgroups of disease and suggest new targeted therapeutic approaches.
authors.affiliation: MRC Toxicology Unit and Department of Cancer Studies and Molecular Medicine, University of Leicester, Lancaster Road, Leicester, United Kingdom. mjsd1@le.ac.uk
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Melania
authors.initials: M
authors.lastname: Capasso
authors.forename: Palminder
authors.initials: P
authors.lastname: Dusanjh
authors.forename: Yin Fai
authors.initials: YF
authors.lastname: Lee
authors.forename: E Loraine
authors.initials: EL
authors.lastname: Karran
authors.forename: Inga
authors.initials: I
authors.lastname: Nagel
authors.forename: Inga
authors.initials: I
authors.lastname: Vater
authors.forename: Gunnar
authors.initials: G
authors.lastname: Cario
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
mesh_terms: D000208:Acute Disease; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D051796:Inhibitor of Differentiation Proteins / Q000096:biosynthesis / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D011379:Prognosis; D040641:Quantitative Trait Loci; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000096:biosynthesis / Q000235:genetics; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D007143:Immunoglobulin Heavy Chains; D051796:Inhibitor of Differentiation Proteins; D015514:Oncogene Proteins, Fusion; D018121:Receptors, Cytokine; D017467:Receptors, Erythropoietin; C498762:CRLF2 protein, human; C490128:ID4 protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein