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. 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. 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). The combined use of metformin with chemotherapy is effective in patients with elevated levels of ABCB1 gene expression. Trial registration NCT 03118128: NCT

Polyvinyl alcohol (PVA) hydrogels have a wide range of applications in the pharmaceutical and biomedicine fields due to their exceptional biophysical properties. The study focuses on preparing and characterizing capsule-shaped PVA hydrogels to enhance their biocompatibility and porosity for controlled glucose release and cell proliferation. The hydrogels were prepared using different concentrations (Cs) and molecular weights (MWs) of PVA, with two different lengths, A (10 mm) and B (20 mm), to control glucose release over 60 min. The preparation process involved PVA gel preparation and PVA hydrogel formation. A total of 500 µL of glucose was injected into all dehydrated hydrogels in groups A and B. Glucose release was studied by immersing the hydrogels in saline at 37 °C with stirring at 500 rpm. The SUP-B15 cell line was grown in six A1 hydrogels for biocompatibility testing. The results indicate that all hydrogels remained stable at 37 °C without degrading. Those with a higher C and MW exhibited a denser and less porous structure, lower glucose storage capacity, and higher elongation at break. Significant differences in glucose release, diffusion speed, and flux were observed, which were more evident in A1 > A4, B1 > B4, and B1 > A1 over 60 min. A1 and B1 had higher values because their higher porosity distribution allowed glucose to diffuse more easily. B1, being larger, has more glucose due to its increased length. The cell growth response and viability at 48 h in contact with the hydrogels was similar to that of the control (4.5 × 10⁵ cells/mL, 98.5% vs. 4.8 × 10⁵ cells/mL, 99.7% viability), thus demonstrating biocompatibility. The hydrogels effectively released glucose over 60 min, with variations based on porosity, C, MW, and length, and demonstrated good biocompatibility with the cell line.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignant lymphoid neoplasm and is the most common subtype of non-Hodgkin lymphoma in adults. More than half of patients with DLBCL can achieve remission with standard R-CHOP regimes; however, approximately 30– 40% of patients are still failing this standard therapy, which remains as an important cause of progression and mortality of this disease. It is necessary to have diagnostic and monitoring tools that allow us to improve the accuracy of prognosis in these patients. Circulating tumor cells (CTCs) identification through molecular biomarkers is one of the novel strategies that have been used in other types of cancer, and we aim to use this tool to analyze the potential role in DLBCL. Patients and Methods: We analyzed 138 blood samples of patients with DLBCL, of which CTCs were isolated by density gradient for subsequent detection and quantitation of molecular biomarkers using RT-qPCR with TaqMan probes. Survival analysis was performed using Kaplan–Meier curves. Results: We found overexpression of ABCB1, αSMA, BCL2, BCL6 and VEGFR1 genes, as well as the presence of CK19, EpCAM, KI67, MAGE-A4, SNAIL and TWIST1 genes. CK19 and EpCAM expression were associated with a minor OS (85.7% vs 98.1%, p = 0.002). The overexpression of BCL2, BCL6, VEGFR1 and TWIST1 was related to a minor EFS (p = 0.001). Conclusion: This study showed that in liquid biopsies analyzed, the presence of CTCs can be confirmed through molecular biomarkers, and it has an impact on OS and EFs, making this detection useful in the follow-up and prognosis of patients with DLBCL.

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.

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.

Background/Objectives: The prognosis of acute lymphoblastic leukemia has significantly improved with the incorporation of innovative therapies such as immunotherapy, tyrosine kinase inhibitors, and CAR-T cell-based treatments. Drug resistance, mediated by genes such as ABCB1, has been associated with reduced treatment efficacy in various clinical scenarios. Although measurable residual disease (MRD) is the most reliable tool for monitoring treatment response in acute lymphoblastic leukemia, the relationship between ABCB1 expression and MRD remains unclear. Aims: To evaluate the expression of the ABCB1 resistance gene and explore its potential relationship with measurable residual disease. Methods: Prospective cohort where 57 patients with de novo diagnosis of acute lymphoblastic leukemia were admitted to the Hospital General de México “Dr. Eduardo Liceaga” between 2022 and 2024. Results: A total of 57 patients undergoing chemotherapy-based treatment were included, with a majority being male (n = 30, 52.6%) and a mean age of 32 years (range 18–71 years). Analysis of ABCB1 gene expression revealed that 35.1% (n = 20) had low expression, 40.4% (n = 23) had overexpression, and 24.6% (n = 14) showed absent expression. No statistically significant association was identified between MRD positivity and the presence of the Philadelphia chromosome (p = 0.171, 95% CI) or the ABCB1 high-risk group (high or absent expression) (p = 0.538, 95% CI). Conclusions: Although ABCB1 expression remains a valuable tool for understanding drug resistance in acute lymphoblastic leukemia, this study did not identify a significant relationship with MRD. MRD continues to be the most reliable prognostic factor in chemotherapy-based treatments for acute lymphoblastic leukemia, underscoring its importance in personalized medicine.