Asynchronous expression of myeloid antigens in leukemic cells in a PML/RARalpha transgenic mouse model

Autor(es)

B.A.A. Santana ; M.C. Pintão ; R.S. Abreu e Lima ; P.S. Scheucher ; G.A.S. Santos ; A.B. Garcia ; R.P. Falcão ; E.M. Rego

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 39, n. 5, p. 615-620, Maio 2006.

Resumo

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 a (RARa) and the promyelocytic leukemia (PML) genes on chromosomes 17 and 15, respectively. The expression of the PML/RARa fusion gene is essential for APL genesis. In fact, transgenic mice (TM) expressing PML/RARa 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/RARa 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/RARa TM present a specific immunophenotype. (AU)

• Processo FAPESP: 01/07974-3 - Determinação do efeito da inativação do gene proteína ligante do enhancer CCAAT (C/EBPa) na hematopoese de animais transgênicos PML-RARa
• Beneficiário: Barbara Amélia Aparecida Santana Lemos
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 01/08693-8 - Determinação do efeito da inativação do gene da proteína ligante do enhancer CCAAT (C/EBPa) na hematopoese de animais transgênicos PML-RARa
• Beneficiário: Eduardo Magalhães Rego
• Linha de fomento: Auxílio à Pesquisa - Regular