title: Myeloid leukemia with promyelocytic features in transgenic mice expressing hCG-NuMA-RARalpha.
abstract: Acute promyelocytic leukemia (APL) is characterized by the accumulation of abnormal promyelocytes in the bone marrow (BM), and by the presence of a reciprocal chromosomal translocation involving retinoic acid receptor alpha (RARalpha). To date, five RARalpha partner genes have been identified in APL. NuMA-RARalpha was identified in a pediatric case of APL carrying a translocation t(11;17)(q13;q21). Using a construct containing the NuMA-RARalpha fusion gene driven by the human cathepsin G promoter (hCG-NuMA-RARalpha), two transgenic mouse lines were generated. Transgenic mice were observed to have a genetic myeloproliferation (increased granulopoiesis in BM) at an early age, and rapidly developed a myeloproliferative disease-like myeloid leukemia. This leukemia was morphologically and immunophenotypically indistinguishable from human APL, with a penetrance of 100%. The phenotype of transgenic mice was consistent with a blockade of neutrophil differentiation. NuMA-RARalpha is therefore sufficient for disease development in this APL model.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mahadeo A
authors.initials: MA
authors.lastname: Sukhai
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wu
authors.forename: Yali
authors.initials: Y
authors.lastname: Xuan
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Reis
authors.forename: Karina
authors.initials: K
authors.lastname: Dubé
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Rego
authors.forename: Mantu
authors.initials: M
authors.lastname: Bhaumik
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Bailey
authors.forename: Richard A
authors.initials: RA
authors.lastname: Wells
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear; D001483:Base Sequence; D056649:Cathepsin G; D002403:Cathepsins / Q000235:genetics*; D018797:Cell Cycle Proteins; D017931:DNA Primers; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D012697:Serine Endopeptidases
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D017931:DNA Primers; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; C489080:Numa1 protein, mouse; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534096:Ctsg protein, mouse