Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients’ samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-β, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs’ roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.
Objective: This study describes the hematological parameters associated with the BCR-ABL gene transcripts in patients with chronic myeloid leukemia (CML). Methods: We reviewed the results of 100 detectable patients for one of the BCR-ABL gene transcripts. The eligibility criteria were based on the presence of one of the leukemic transcripts (b2a2, b3a2, and b2a2/b3a2) and complete epidemiological and hematological data. The data were obtained from the LabMaster computerized system. The Kruskal-Wallis test was used to compare the medians of the quantitative variables between the transcripts of the BCR-ABL gene and the chi-square test to compare the qualitative ones, adopting the p-value with a level of significance less than or equal to 0.05. Results: Forty-five patients (45%) presented the b2a2 transcript, 24 (24%) the b3a2 transcript and 31 (31%) a b2a2/b3a2 coexpression. Individuals who expressed the b3a2 transcript had higher leukocyte counts and platelet levels, but we found no differences compared with individuals who expressed the other transcript. Conclusion: In this study, the BCR-ABL gene transcripts did not influence the hematological parameters of patients with CML.
Reference genes are used as internal reaction control for gene expression analysis and for this they are considered reliable and must meet several important criteria. In view of the absence of studies regarding the best reference gene for the analysis of acute leukemia patients, a panel of genes commonly used as endogenous was selected from the literature for analysis of stability: GAPDH, ABL, HPRT1, RPLP0, ACTB and TBP. The stability of candidate reference genes was analyzed according to four statistical methods of assessment, namely, NormFinder, GeNorm and R software. From this study’s analysis it was possible to identify that the endogenous set composed by ACTB, ABL, TBP and RPLPO demonstrated good performances and stable expressions between the analyzed groups. Besides that, the GAPDH and HPRT genes could not be classified as good reference genes, considering that they presented a high standard deviation and great variability between groups, indicating low stability. Given these findings, this study suggests the main endogenous set for use as control/reference for the analysis of gene expression in peripheral blood and bone marrow samples from patients with acute leukemias, is composed by the ACTB, ABL, TBP and RPLPO genes.
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