Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) represents around 25% of adult acute leukemias. Despite the increasing improvement in the survival rate of ALL patients during the last decade, the heterogeneous clinical and molecular features of this malignancy still represent a major challenge for treatment and achieving better outcomes. To identify aberrantly expressed genes in bone marrow (BM) samples from adults with ALL, transcriptomic analysis was performed using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0). Differentially expressed genes (DEGs) (±2-fold change, p-value < 0.05, and FDR < 0.05) were detected using the Transcriptome Analysis Console. Gene Ontology (GO), Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA) were employed to identify gene function and define the enriched pathways of DEGs. The protein-protein interactions (PPIs) of DEGs were constructed. A total of 871 genes were differentially expressed, and DNTT, MYB, EBF1, SOX4, and ERG were the top five up-regulated genes. Meanwhile, the top five down-regulated genes were PTGS2, PPBP, ADGRE3, LUCAT1, and VCAN. An association between ERG, CDK6, and SOX4 expression levels and the probability of relapse and death was observed. Regulation of the immune system, immune response, cellular response to stimulus, as well as apoptosis signaling, inflammation mediated by chemokines and cytokines, and T cell activation were among the most altered biological processes and pathways, respectively. Transcriptome analysis of ALL in adults reveals a group of genes consistently associated with hematological malignancies and underscores their relevance in the development of ALL in adults.

Effect of a Cross-Training and Resistance Exercise Routine on IL-15 in Adults with Type B Acute Lymphoblastic Leukemia during the Induction Phase: Randomized Pilot Study.

IL-15 is a proinflammatory myokine essential for activating NK cells and CD8+ T lymphocytes, and its overexpression has been related to reducing overall survivorship in patients with acute lymphoblastic leukemia (ALL). Physical exercise has been shown to be safe, feasible, and beneficial in hematological cancers. Exercise requires the activation of muscles that secrete cytokines, such as IL-15, causing immune mobilization. The objective was to compare the outcomes of two training routines on IL-15 and survival prognosis in adult patients diagnosed with ALL. A blind randomized clinical study was carried out where twenty-three peripheral blood samples were obtained pre and postexercise intervention from patients categorized into three types of intervention: the resistance exercise group (REG), the cross-training exercise group (CEG), and the control group (CG). Changes in IL-15 levels during the intervention were not significant in any of the groups (CG p = 0.237, REG p = 0.866, and CEG p = 0.678). However, 87.5% of patients who received an exercise intervention achieved remission, while only 21.73% experienced a relapse. There were no deaths during the study. Although IL-15 level adaptation in the REG and the CG performed similarly, the REG induced a better clinical outcome. Resistance exercises may help improve survival prognosis and reduce relapses in patients with ALL.

Impact of the ABCB1 Drug Resistance Gene on the Risk Factors of Patients with COVID-19 and Its Relationship with the Drugs Used.

Objective: In the last two years progress was made in molecular, physio pathological understanding and the form of transmission of COVID-19, and different therapeutic strategies have been explored to deal with the situation of the pandemic. However, the evaluation of certain genes that participate in the metabolism and transport of these drugs has not been fully explored. A lack of response to treatment and a lower survival have been observed that may be due to the presence of the ABCB1 drug resistance gene. Our research group analyzed whether the expression levels of the ABCB1 gene are associated with comorbidities, treatments, overall survival and risk of death in patients with severe COVID-19. Methods: The expression levels of the ABCB1 gene were analyzed by RT-qPCR in 61 patients diagnosed with COVID-19. The association between the levels of expression, the risk variables and different treatments were determined by the Chi-Square test and the Fisher's exact test. Global Survival (GS) was determined by the Kaplan-Meier method. The impact of high levels of expression and the risk of death was performed by odds ratio. Results: The different risk variables showed that patients with either high or absent levels of ABCB1 gene expression presented a greater risk of death (OR 3.08, 95%, CI 1.02-9.26) as well as need for ventilatory support (OR 2.8, 95%, CI 0.98 -8.5). Patients with diabetes and COVID-19, treated with metformin, were associated with a lower risk of death (OR 1.11, 95%, CI 0.38-3.22). OS with respect to high or absent levels of expression of the ABCB1 gene was lower. Conclusion: High levels or null expression of the ABCB1 gene are associated with a higher risk of death or progression of the disease, the use of metformin in patients with COVID-19 confers a lower risk of death.

[Effect of metformin added to chemotherapy on the survival of patients with acute lymphoblastic leukemia]. / Efecto de la metformina en la etapa de inducción en pacientes con leucemia aguda linfoblástica y su impacto clínico en la supervivencia.

BACKGROUND: Metformin has antineoplastic and cancer protective effects in vitro, sensitizing leukemia cells to chemotherapeutic agents, inducing apoptosis and cell cycle arrest. AIM: To assess the effect of metformin on the induction stage in patients with ALL and its impact on overall survival and relapse. MATERIAL AND METHODS: We included 123 patients treated with metformin and without metformin. The dose used was 850 mg PO at 8 h intervals. The survival analysis was used by Kaplan-Meier method, the difference between the distinct groups was performed using the log Rank test. RESULTS: The overall survival at a median follow up of 700 days of follow-up was 43%, with a disease-free survival of 47%. Regarding the treatment groups, patients with metformin had a lower rate of relapse compared to the group receiving only chemotherapy (6.5% vs 17.1%, p = 0.006). CONCLUSIONS: The addition of metformin to the conventional treatment of ALL was associated with an improvement in survival, this association being independent of the type of biological risk at diagnosis.

Effect of metformin on the survival of patients with ALL who express high levels of the ABCB1 drug resistance gene.

BACKGROUND: In acute lymphoblastic leukemia (ALL), high ABCB1 gene expression has been associated with treatment resistance, which affects patient prognosis. Many preclinical reports and retrospective population studies have shown an anti-cancer effect of metformin. Therefore, the objective of this study was to assess the effect of metformin on the treatment regimen in patients with ALL who exhibited high levels of ABCB1 gene expression and to determine its impact on overall survival. METHODS: A total of 102 patients with ALL were recruited; one group (n = 26) received metformin, and the other received chemotherapy (n = 76). Measurement of ABCB1 transcript expression was performed using qRT-PCR prior to treatment initiation. Survival analysis was performed using Kaplan-Meier curves. The impact of both the type of treatment and the level of expression on the response (remission or relapse) was analyzed by calculating the odds ratio. RESULTS: The survival of patients with high ABCB1 expression was lower than those with low or absent ABCB1 gene expression (p = 0.030). In the individual analysis, we identified a benefit to adding metformin in the group of patients with high ABCB1 gene expression (p = 0.025). In the metformin user group, the drug acted as a protective factor against both therapeutic failure (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.0037-1.53) and early relapse (OR 0.05, 95% CI 0.0028-1.153). CONCLUSION: The combined use of metformin with chemotherapy is effective in patients with elevated levels of ABCB1 gene expression. Trial registration NCT 03118128: NCT.

Efecto de la metformina en la etapa de inducción en pacientes con leucemia aguda linfoblástica y su impacto clínico en la supervivencia / Effect of metformin added to chemotherapy on the survival of patients with acute lymphoblastic leukemia

Background: Metformin has antineoplastic and cancer protective effects in vitro, sensitizing leukemia cells to chemotherapeutic agents, inducing apoptosis and cell cycle arrest. Aim: To assess the effect of metformin on the induction stage in patients with ALL and its impact on overall survival and relapse. Material and Methods. We included 123 patients treated with metformin and without metformin. The dose used was 850 mg PO at 8 h intervals. The survival analysis was used by Kaplan-Meier method, the difference between the distinct groups was performed using the log Rank test. Results. The overall survival at a median follow up of 700 days of follow-up was 43%, with a disease-free survival of 47%. Regarding the treatment groups, patients with metformin had a lower rate of relapse compared to the group receiving only chemotherapy (6.5% vs 17.1%, p = 0.006). Conclusions. The addition of metformin to the conventional treatment of ALL was associated with an improvement in survival, this association being independent of the type of biological risk at diagnosis.