Abnormal expression of H-Ras induces S-phase arrest and mitotic catastrophe in human T-lymphocyte leukemia

Leukemia is a neoplasm with high incidence and mortality rates. Mitotic death has been observed in tumor cells treated with chemotherapeutic agents. Ras family proteins participate in the transduction of signals involved in different processes, such as proliferation, differentiation, survival, and p...

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Published in:Blood research Vol. 58; no. 1; pp. 20 - 27
Main Authors: Zamora Dominguez, Jorge Antonio, Olarte Carrillo, Irma, Ruiz Ramos, Rubén, Ramos-Peñafiel, Christian Omar, Jiménez Zamudio, Luis, García Latorre, Ethel, Centeno Cruz, Federico, Martínez Tovar, Adolfo
Format: Journal Article
Language:English
Published: Korea (South) Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis 31-03-2023
대한혈액학회
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Summary:Leukemia is a neoplasm with high incidence and mortality rates. Mitotic death has been observed in tumor cells treated with chemotherapeutic agents. Ras family proteins participate in the transduction of signals involved in different processes, such as proliferation, differentiation, survival, and paradoxically, initiation of cell death. This study investigated the effect of expression on human T-cell acute lymphoblastic leukemia MOLT-4 cells. Cells were electroporated with either wild-type (Ras ) or oncogenic mutant in codon 12 exon 1 (Ras ) versions of gene and stained for morphological analysis. Cell viability was assessed using trypan blue staining and cell cycle analysis using flow cytometry. gene expression was determined using quantitative real-time reverse transcription polymerase chain reaction. The , ANOVA, and Scheffe tests were used for statistical analysis. Human T-cell acute lymphoblastic leukemia MOLT-4 cells showed nuclear fragmentation and presence of multiple nuclei and micronuclei after transfection with either wt or mutant genes. Cell cycle analysis revealed a statistically significant increase in cells in the S phase when transfected with either wt (83.67%, <0.0005) or mutated (81.79%, <0.0001) genes. Although similar effects for both versions of were found, cells transfected with the mutated version died at 120 h of mitotic catastrophe. Transfection of human T-cell acute lymphoblastic leukemia MOLT-4 cells with either normal or mutated genes induced alterations in morphology, arrest in the S phase, and death by mitotic catastrophe.
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ISSN:2287-979X
2288-0011
DOI:10.5045/br.2023.2022143