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.
Highlights
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myelogenous leukemia invariably associated with recurrent chromosomal translocations involving the retinoic acid receptor α (RARα) locus on chromosome 17 [1]
Several groups have used the human cathepsin G minigene to drive the expression of promyelocytic leukemia locus (PML)/RARα to the promyelocytic stage of myeloid differentiation, and these transgenic mouse (TM) develop a lethal form of leukemia that closely resembles human APL [8,9]
Overt acute leukemia occurred after a long pre-leukemic phase (12-15 months) and affected only 10 to 15% of the TM, suggesting that PML/ RARα is necessary but not sufficient for full-blown leukemogenesis
Summary
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myelogenous leukemia invariably associated with recurrent chromosomal translocations involving the retinoic acid receptor α (RARα) locus on chromosome 17 [1]. Several groups have used the human cathepsin G (hCG) minigene to drive the expression of PML/RARα to the promyelocytic stage of myeloid differentiation, and these TM develop a lethal form of leukemia that closely resembles human APL [8,9]. Leukemic cells of hCG-PML/RARα TM are morphologically similar to human promyelocytes, their immunophenotypic features have not been fully characterized.
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More From: Brazilian Journal of Medical and Biological Research
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