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Asynchronous expression of myeloid antigens in leukemic cells in a PML/RARalpha transgenic mouse model
B A A Santana1, M C Pintão, R S Abreu e Lima
1Divisão 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.
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.
Insights
Transgenic mice expressing the PML/RARalpha fusion gene develop acute promyelocytic leukemia (APL). Leukemic cells in these mice exhibit a specific immunophenotype, mirroring human APL.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Acute promyelocytic leukemia (APL) is a distinct subtype of leukemia characterized by specific genetic alterations.
- The PML/RARalpha fusion gene, resulting from a chromosomal translocation, is crucial for APL development.
- Transgenic mouse models expressing PML/RARalpha mimic human APL, but their leukemic cell immunophenotype requires detailed characterization.
Purpose of the Study:
- To characterize the immunophenotype of leukemic cells in a transgenic mouse model of acute promyelocytic leukemia (APL).
- To investigate the expression of myeloid antigens on leukemic cells in hCG-PML/RARalpha transgenic mice.
- To compare the immunophenotype of leukemic cells in the mouse model with that of human APL.
Main Methods:
- Morphological analysis of bone marrow from transgenic mice (TM) at different stages of leukemia development.
- Flow cytometry analysis of bone marrow and spleen cells from leukemic TM to assess myeloid antigen expression.
- Comparison of immunophenotypic data between leukemic TM, pre-leukemic TM, and wild-type controls.
Main Results:
- Transgenic mice expressing PML/RARalpha developed leukemia with a significant increase in immature myeloid cells.
- Leukemic cells in TM exhibited asynchronous co-expression of CD34, CD117, and CD11b.
- This abnormal immunophenotype was specific to the leukemic phase and not detected in pre-leukemic or control mice.
Conclusions:
- Leukemic cells in the hCG-PML/RARalpha transgenic mouse model display a distinct and specific immunophenotype.
- This immunophenotype closely resembles that observed in human acute promyelocytic leukemia.
- The transgenic mouse model serves as a valuable tool for studying APL pathogenesis and potential therapeutic strategies.
