ANALYSIS OF THE EXPRESSION PATTERN OF CELL CYCLE AND TUMOR SENESCENCE REGULATORY GENES IN HTLV-1 CARRIERS AND ADULT T-CELL LEUKEMIA/LYMPHOMA PATIENTS

Autor: HF Culler, RJ Filho, CO Reichert, FA Freitas, K Marques, Y Nukui, VG Rocha, LAPC Lage, J Pereira
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Hematology, Transfusion and Cell Therapy, Vol 46, Iss , Pp S261-S262 (2024)
Druh dokumentu: article
ISSN: 2531-1379
DOI: 10.1016/j.htct.2024.09.437
Popis: Introduction: Infection with Human T-Lymphotropic Virus Type 1 (HTLV-1) is endemic in various regions worldwide. Brazil has an estimated 800,000 to 2.5 million infected individuals. This virus is associated with a broad spectrum of clinical manifestations, ranging from asymptomatic infection to severe diseases such as tropical spastic paraparesis/HTLV-1-associated myelopathy (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Both conditions are linked to high morbidity and mortality. HTLV-1 can infect and alter the function of immune system cells, particularly CD4+ T lymphocytes, causing abnormalities in genes involved in cellular senescence, proliferation, and apoptosis. This study aimed to evaluate the differential expression of genes regulating senescence and cellular proliferation in asymptomatic HTLV-1 carriers. Methods: Peripheral blood samples were collected from healthy individuals (controls), asymptomatic HTLV-1 carriers, and ATLL patients. Gene expression analysis was performed using RNA extracted from CD4+ T lymphocytes separated by magnetic microbeads. The extracted RNA was converted into cDNA for quantitative real-time polymerase chain reaction (qRT-PCR). Results: A total of 32 asymptomatic HTLV-1 carriers, 30 healthy controls, and 7 ATLL cases were analyzed (N = 69). Of the 32 asymptomatic HTLV-1 carriers, 22 (68.8%) were female; in the control group, 16 (53.3%) were female, and in the ATLL group, 5 (71.4%) were female. The age of asymptomatic HTLV-1 carriers ranged from 20 to 87 years (median 58 years), from 31 to 66 years (median 52 years) in the control group, and from 43 to 79 years (median 64 years) in the ATLL group. Three (43%) patients were classified as having smouldering ATLL, and 1 (14.3%) as acute ATLL. The genes CDKN1A, PIK3CA, and RBL2 were underexpressed in asymptomatic HTLV-1 carriers. ATLL patients exhibited underexpression of CDKN1A and overexpression of COL3A1. Conclusion: Asymptomatic HTLV-1 carriers showed underexpression of CDKN1A, PIK3CA, and RBL2 in CD4+ T lymphocytes. CDKN1A was also significantly underexpressed in ATLL. Asymptomatic carriers and ATLL patients did not show differential expression of the genes AKT1, ID1, IFNG, NFKB1, PTEN, TERT, TWIST1, and SPARC. COL3A1 was overexpressed in ATLL patients.
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