The human induced pluripotent stem cells (hiPSCs) are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

We analyzed cytogenetically 105 patients with hypocellular primary MDS and their clinical implications. The main chromosomal abnormalities found were del(5q)/−5, del(6q)/+6, del(7q)/−7, del(11q), and del(17p). Pediatric patients had a higher frequency of abnormal karyotypes compared with adult patients (P< 0,05). From our patients, 18% showed evolution of the disease. The chromosomal abnormalities presented in the diagnosis of patients who evolved to AML included numerical (−7, +8) and structural del(6q), del(7q), i(7q), t(7;9), i(9q), and del(11q) abnormalities and complex karyotypes. Although the frequency of evolution from hypocellular MDS to AML is low, our results suggest that some chromosomal alterations may play a critical role during this process. We applied the IPSS in our patients because this score system has been proved to be useful for predicting evolution of disease. When we considered the patients according to group 1 (intermediate-1) and group 2 (intermediate-2 and high risk), we showed that group 2 had a high association with respect to the frequency of abnormal karyotypes (P< 0,0001), evolution of disease (P< 0,0001), and mortality (P< 0,001). In fact, the cytogenetic analysis for patients with hypocellular primary MDS is an important tool for diagnosis, prognosis, in clinical decision-making and in follow-up.

Introduction: The objective of the current study was to determine the survival probabilities of children and adolescents with acute lymphocytic leukemia treated with adapted Berlin–Frankfurt–Münster (BFM) protocols and compare our results with the original BFM reports. Methods: This retrospective study included 695 patients up to 19 years old treated with adapted BFM protocols between 1997 and 2018 in four hospitals in Rio de Janeiro. The 1997–2007 and 2008–2018 cohorts were analyzed separately. Results: More than half of the patients were stratified into the high-risk BFM classification. Overall and event-free survivals were, in the 1997–2007 period, respectively, 88% and 80% (BFM standard risk group—SRG), 75% and 67% (intermediate risk group—IRG), and 48% and 33% (high-risk group—HRG). The corresponding numbers for the 2008–2018 period were 93% and 84% (SRG), 75% and 63% (IRG), and 64% and 57% (HRG). In the second period, both the OS (HR = 0.71, p = 0.011) and EFS (HR = 0.62, p < 0.001) were higher. Except for the intermediate-risk group, the latter results are comparable to the BFM. Conclusion: The BFM protocol adaptations can be safely implemented in developing countries, accounting for local specificities.

This systematic review assessed the impact of CYP3A5, CYP3A4, and ABCB1 polymorphisms on the pharmacokinetics and clinical outcomes of calcineurin inhibitors in hematopoietic cell transplantation (HCT) recipients. Following PRISMA 2020 guidelines, the protocol was registered in PROSPERO (CRD42024517094). A comprehensive search in PubMed, BVS, Scopus, Web of Science, Embase, and Cochrane databases (2013–2024) identified observational studies focusing on tacrolimus or cyclosporine and the specified polymorphisms. Studies on non-human subjects, solid organ transplants, pharmacokinetic models, and drug interactions were excluded. Narrative synthesis was employed due to heterogeneity, and study quality was evaluated using the Newcastle–Ottawa Scale (NOS) and STREGA guidelines. Of 301 records, 11 studies met inclusion criteria, predominantly retrospective and involving adult populations, with sample sizes ranging from 20 to 420 HCT recipients from the USA, Japan, and France. Outcomes included drug levels, median concentration/dose (C/D) ratio, therapeutic index, and clinical endpoints such as graft-versus-host disease (GVHD) and acute kidney injury (AKI). CYP3A5*3 (rs776746) significantly influenced tacrolimus levels, C/D ratio, and clinical outcomes, highlighting its potential as a pharmacogenetic biomarker. CYP3A4 and ABCB1 polymorphisms demonstrated limited effects on tacrolimus pharmacokinetics and no significant clinical impact. Methodological quality was high, with 55% of studies achieving the maximum NOS score, although gaps in error rates and population modeling were noted. Limitations include variability in outcomes precluding meta-analysis, a small number of studies, particularly on cyclosporine, and insufficient data on CYP3A4 and ABCB1. Further research is necessary to validate findings.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024517094, PROSPERO, CRD42024599998.

Purpose: The aim of this study was to analyse the expression profiles of DNMT1, DNMT3A, DNMT3B (components of DNA methylation machinery), TET2 and APOBEC3B (components of DNA demethylation machinery) in pediatric MDS patients and investigate their associations with MDS subtypes, cytogenetics, evolution to acute myeloid leukemia (AML) and p15^INK4B methylation level. Patients and Methods: The expressions of DNMT1, DNMT3A, DNMT3B, TET2, and APOBEC3B were evaluated in 39 pediatric MDS patients by real-time quantitative PCR (qPCR). The quantification of p15^INK4B methylation levels (MtL) was performed in 20 pediatric MDS patients by pyrosequencing. Mann–Whitney test was used to evaluate possible differences between the expression levels of selected in patients and donors, according to MDS subtypes, karyotypes, evolution to AML and p15^INK4B MtL. The correlations between the expression levels of the different genes were assessed by Spearman rank correlation coefficient. Results: We found that DNMTs expression levels were higher in pediatric MDS compared to donors [DNMT1 (p< 0.03), DNMT3A (p< 0.03), DNMT3B (p< 0.02)]. TET2 and APOBEC3B expression levels did not show a statistically significant difference between pediatric patients and donors. Considering MDS subtypes, patients at initial stage presented DNMT1 overexpression (p< 0.01), while DNMT3A (p< 0.02) and DNMT3B (p< 0.007) were overexpressed in advanced subtypes. TET2 and APOBEC3B expression did not differ in MDS subtypes. DNMT1 (p< 0.03), DNMT3B (p< 0.03), and APOBEC3B (p< 0.04) expression was higher in patients with normal karyotypes, while patients with abnormal karyotypes showed higher DNMT3A expression (p< 0.03). Karyotypes had no association with TET2 expression. DNMTs overexpression was observed in patients who showed disease evolution. A positive correlation was found between DNMTs expression and between APOBEC3B and DNMT3A/DNMT3B. However, TET2 expression was not correlated with DNMTs or APOBEC3B. p15^INK4B MtL was higher in pediatric MDS patients compared with donors (p< 0.03) and its hypermethylation was associated with increased DNMT1 expression (p< 0.009). Conclusion: Our results suggest that the overexpression of DNMTs and an imbalance between the expressions of the DNA methylation/demethylation machinery components play an important role in MDS development and evolution to AML. These results have clinical implications indicating the importance of DNMTs inhibitors for preventing or delaying the progression to leukemia in pediatric MDS patients.