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

Brazilian Journal of Medical and Biological Research

B.a.a. Santana¹  M.c. Pintão¹  R.s. Abreu E Lima¹  P.s. Scheucher¹  G.a.s. Santos¹  A.b. Garcia¹  R.p. Falcão¹  E.m. Rego¹ 

[1] ,Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de Clínica MédicaRibeirão Preto SP ,Brasil

关键词: Acute promyelocytic leukemia;    Acute myelogenous leukemia;    Transgenic mice;    Flow cytometry;    Leukemogenesis;   

DOI  :  10.1590/S0100-879X2006000500008

来源: SciELO

【 摘 要 】

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.

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