Unveiling Myelodysplastic Syndromes: Exploring Pathogenic Mechanisms and Therapeutic Advances

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 508 - 508

Published: Feb. 3, 2025

Myelodysplastic syndromes (MDSs), either primary or secondary, are a heterogeneous group of clonal hematological neoplasms characterized by bone marrow dyshematopoiesis, peripheral blood cytopenia, and the potential risk acute myeloid leukemia (AML) transformation. The clinical heterogeneity in MDS is reflection underlying multitude genetic defects playing role pathogenesis. Recent advances clinicopathological, immunophenotypic, molecular landscape understanding pathophysiology lead to evolving refined classification systems with newer entities. Evolving therapies will target disease’s core mechanisms, allowing for personalized treatment based on individual patient’s genes leading better outcomes. This review provides an overview pathogenesis enhance comprehension its various subgroups. Additionally, we examine updated World Health Organization (WHO) International Consensus Classification (ICC) pertaining MDS, along relevant therapeutic approaches.

Language: Английский

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Safety profiles of IDH inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database

Future Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 6, 2025

Abstract Background With the increased use of isocitrate dehydrogenase (IDH) inhibitors in acute myeloid leukemia (AML) and cholangiocarcinoma, toxicity these drugs is a growing concern. This study aimed to evaluate adverse events (AEs) IDH based on Food Drug Administration Adverse Event Reporting System (FAERS) database. Methods AE reports for (enasidenib, ivosidenib, olutasidenib) were collected analyzed from time launch through first quarter 2024. Only reported as target drug coded primary suspect (PS) included analysis. AEs standardized classified according preferred term (PT) system organ classification (SOC) Medical Dictionary Regulatory Activities (MedDRA) version 26.0. Disproportionality analyses including reporting odds ratio Bayesian confidence propagation neural network performed data mining assess inhibitor-relatedAEs. Differentiation syndrome was special interest. Results The number enasidenib, olutasidenib 11 616 357, 10 067 250, 2 563 464, respectively. A total 80 enasidenib-related signals involving 15 SOCs, 78 ivosidenib-related 17 7 olutasidenib-related 4 SOCs obtained. most “blood lymphatic disorders,” “infections infestations,” “nervous disorders” enasidenib. For frequently “gastrointestinal “general disorders administration site conditions,” “injury, poisoning procedural complications.” Ivosidenib only inhibitor with “cardiac disorders.” 89, 40, cases olutasidenib, median onset 26–31 days ivosidenib AML common indication differentiation reports. Conclusions Our identifies potential associated provides broader understanding safety. safety profiles highlight need long-term monitoring recipients. Promptly intervention specific systems depending type may improve overall survival or enhance quality life. In future, it will be necessary validate our findings prospective large-scale studies investigate underlying mechanisms.

Language: Английский

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Genetic Profiling of Acute and Chronic Leukemia via Next-Generation Sequencing: Current Insights and Future Perspectives

Hematology Reports, Journal Year: 2025, Volume and Issue: 17(2), P. 18 - 18

Published: March 28, 2025

Leukemia is a heterogeneous group of hematologic malignancies characterized by distinct genetic and molecular abnormalities. Advancements in genomic technologies have significantly transformed the diagnosis, prognosis, treatment strategies for leukemia. Among these, next-generation sequencing (NGS) has emerged as powerful tool, enabling high-resolution profiling that surpasses conventional diagnostic approaches. By providing comprehensive insights into mutations, clonal evolution, resistance mechanisms, NGS revolutionized precision medicine leukemia management. Despite its transformative potential, clinical integration presents challenges, including data interpretation complexities, standardization issues, cost considerations. However, continuous advancements platforms bioinformatics pipelines are enhancing reliability accessibility routine practice. The expanding role paving way improved risk stratification, targeted therapies, real-time disease monitoring, ultimately leading to better patient outcomes. This review highlights impact on research applications, discussing advantages over traditional techniques, key approaches, emerging challenges. As oncology continues evolve, expected play an increasingly central diagnosis management leukemia, driving innovations personalized therapeutic interventions.

Language: Английский

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Synergistic Strategies for KMT2A-Rearranged Leukemias: Beyond Menin Inhibitor

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 4017 - 4017

Published: Nov. 29, 2024

KMT2A-rearranged leukemias are a highly aggressive subset of acute leukemia, characterized by poor prognosis and frequent relapses despite intensive treatment. Menin inhibitors, which target the critical KMT2A-menin interaction driving leukemogenesis, have shown promise in early clinical trials. However, resistance to these often driven menin mutations or alternative oncogenic pathways, remains significant challenge. This review explores combination therapies aimed at overcoming improving patient outcomes. Potential strategies include inhibiting DOT1L, histone methyltransferase essential for KMT2A-driven transcription, BRD4, regulator transcriptional super-enhancers. Additionally, targeting MYC, key oncogene frequently upregulated offers another approach. Direct inhibition KMT2A-fusion proteins c-MYB, transcription factor leukemic stem cell maintenance, is also explored. By integrating diverse strategies, we propose comprehensive therapeutic paradigm that targets multiple points epigenetic network. These approaches aim disrupt reduce resistance, enhance treatment efficacy, ultimately providing more durable remissions improved survival patients with leukemias.

Language: Английский

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