Objective: To explore the expression of the transcription factors LMO2 and LYL1 and the interaction between these 2 factors in myeloid leukemia cells and to analyze the significance thereof in leukemogenesis.
Methods: Samples of peripheral blood and bone marrow were collected form 51 AML patties, and 5 normal bone marrow donors to isolate mononuclear cells (MNCs) with high percentage of CD34(+) cells. Western blotting (WB) was used to detect the protein expression of LMO2 and LYL1 in the cells. Human myeloid leukemia cells of the line K562 were cultured and transfected with pcDNA3-LMO2, plasmid containing LMO2, pcDNA3-LYL1, plasmid containing LYL1, or pcDNA-GFP, blank plasmid containing green fluorescent protein. RT-PCR was used to detect the mRNA expression of LMO2 and LYL1. Co-immunoprecipitation (co-IP) and WB were used to detect the binding protein of LMO2 and LYL1.
Results: The MNCs of 51.1% of the patients with acute myeloblastic leukemia (AML) without remission expressed higher levels of LMO2, the MNCs of 62.2% of the AML patients expressed higher levels of LYL1, and the MNCs of 31.1% of those expressed both. The K562 cells transfected with pcDNA3-LMO2 showed higher mRNA and protein expression levels of both LMO2 and LYL1, and the K562 cells transfected with pcDNA3-LYL1 showed higher mRNA and protein expression levels of both LYL1 and LMO2 too, as indicated by RT-PCR and WB, which suggested that the expression of LMO2 and the expression of LYL1 stimulated each other in the myeloid leukemia cells. Co-IP assay detected the presence of LMO2-LYL1 complex in those cells.
Conclusion: The abnormal expression and protein interaction of LMO2 and LYL1 may play a role in the abnormal proliferation and differentiation of myeloid hematopoietic cells.
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Leukemia
June 2024
Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.
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European Molecular Biology Laboratory, EMBL Rome - Epigenetics and Neurobiology Unit, via E. Ramarini 32, 00015, Monterotondo, Italy.
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School of Medicine, Tsinghua University, Beijing 100084, China.
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