title: Asynchronous expression of myeloid antigens in leukemic cells in a PML/RARalpha transgenic mouse model.
abstract: Acute promyelocytic leukemia (APL) is characterized by the expansion of blasts that resemble morphologically promyelocytes and harbor a chromosomal translocation involving the retinoic acid receptor alpha (RARalpha) and the promyelocytic leukemia (PML) genes on chromosomes 17 and 15, respectively. The expression of the PML/RARalpha fusion gene is essential for APL genesis. In fact, transgenic mice (TM) expressing PML/RARalpha develop a form of leukemia that mimics the hematological findings of human APL. Leukemia is diagnosed after a long latency (approximately 12 months) during which no hematological abnormality is detected in peripheral blood (pre-leukemic phase). In humans, immunophenotypic analysis of APL blasts revealed distinct features; however, the precise immunophenotype of leukemic cells in the TM model has not been established. Our aim was to characterize the expression of myeloid antigens by leukemic cells from hCG-PML/RARalpha TM. In this study, TM (N = 12) developed leukemia at the mean age of 13.1 months. Morphological analysis of bone marrow revealed an increase of the percentage of immature myeloid cells in leukemic TM compared to pre-leukemic TM and wild-type controls (48.63 +/- 16.68, 10.83 +/- 8.11, 7.4 +/- 5.46%, respectively; P < 0.05). Flow cytometry analysis of bone marrow and spleen from leukemic TM identified the asynchronous co-expression of CD34, CD117, and CD11b. This abnormal phenotype was rarely detected prior to the diagnosis of leukemia and was present at similar frequencies in hematologically normal TM and wild-type controls of different ages. The present results demonstrate that, similarly to human APL, leukemic cells from hCG-PML/RARalpha TM present a specific immunophenotype.
authors.affiliation: Divisão de Hematologia e Centro de Terapia Celular, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: B A A
authors.initials: BA
authors.lastname: Santana
authors.forename: M C
authors.initials: MC
authors.lastname: Pintão
authors.forename: R S
authors.initials: RS
authors.lastname: Abreu e Lima
authors.forename: P S
authors.initials: PS
authors.lastname: Scheucher
authors.forename: G A S
authors.initials: GA
authors.lastname: Santos
authors.forename: A B
authors.initials: AB
authors.lastname: Garcia
authors.forename: R P
authors.initials: RP
authors.lastname: Falcão
authors.forename: E M
authors.initials: EM
authors.lastname: Rego
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D056649:Cathepsin G; D002403:Cathepsins; D005434:Flow Cytometry; D005838:Genotype; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534096:Ctsg protein, mouse