Bosco Shinto, Beniwal Shreya Singh, Munshi Samid Soeb, Calderón Daniela Castro, Jeong Yujin, Cacas Alyanna Cabe, Kumar Sandeep, Carvalho Dos Santos Pedro Henrique Serra, Syed Saif, Dwivedi Ayush, Einieh Mahmoud
Dr. D. Y Patil Medical College, Hospital and Research Centre, Dr. D. Y Patil Vidyapeeth (Deemed to be University), Pimpri, Maharashtra, India.
Lady Hardinge Medical College, Connaught Place, New Delhi, India.
Ann Med Surg (Lond). 2025 Aug 19;87(9):5557-5568. doi: 10.1097/MS9.0000000000003365. eCollection 2025 Sep.
Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells characterized by aberrant proliferation of myeloid lineages, driven primarily by mutations in JAK2, CALR, and myeloproliferative leukemia, leading to constitutive activation of the JAK-STAT pathway. Emerging evidence highlights mitochondrial dysfunction as a key factor in MPN pathogenesis, contributing to increased reactive oxygen species production, mitochondrial DNA mutations, and dysregulated mitochondrial dynamics, which collectively promote clonal expansion and apoptosis resistance. Targeting mitochondrial pathways has gained attention as a therapeutic strategy, with approaches including mitochondria-targeted antioxidants, metabolic inhibitors, and modulation of mitophagy and mitochondrial fission/fusion dynamics. However, challenges such as drug delivery specificity, therapeutic resistance, and off-target effects remain significant. Recent advances in precision medicine, incorporating genomic, transcriptomic, and proteomic profiling, offer a more personalized approach to MPN treatment by tailoring interventions to individual mutation patterns. Additionally, novel therapeutic strategies, including gene editing technologies, RNA-based therapies, and nanoparticle-mediated drug delivery systems, hold promise for overcoming current treatment limitations. The integration of artificial intelligence in drug discovery and biomarker identification further enhances the potential for targeted therapies. Future research should focus on refining these strategies, developing reliable biomarkers for patient stratification, and exploring combination therapies that enhance treatment efficacy while minimizing adverse effects. By addressing mitochondrial dysfunction as an underlying driver of MPNs, these emerging approaches have the potential to improve disease management, extend patient survival, and enhance quality of life. Also, this new approach of precision medicine allows patient stratification and ensures that treatments are formed according to the individual disease biology of each patient, which results in overall better outcomes.
骨髓增殖性肿瘤（MPNs）是造血干细胞的克隆性疾病，其特征为髓系谱系的异常增殖，主要由JAK2、CALR和骨髓增殖性白血病的突变驱动，导致JAK-STAT通路的组成性激活。新出现的证据强调线粒体功能障碍是MPN发病机制中的关键因素，导致活性氧生成增加、线粒体DNA突变以及线粒体动力学失调，这些共同促进克隆性扩增和凋亡抵抗。靶向线粒体通路作为一种治疗策略已受到关注，方法包括线粒体靶向抗氧化剂、代谢抑制剂以及对线粒体自噬和线粒体分裂/融合动力学的调节。然而，诸如药物递送特异性、治疗抵抗和脱靶效应等挑战仍然很大。精准医学的最新进展，包括基因组、转录组和蛋白质组分析，通过根据个体突变模式定制干预措施，为MPN治疗提供了更个性化的方法。此外，包括基因编辑技术、基于RNA的疗法和纳米颗粒介导的药物递送系统在内的新型治疗策略有望克服当前的治疗局限性。人工智能在药物发现和生物标志物识别中的整合进一步增强了靶向治疗的潜力。未来的研究应侧重于完善这些策略，开发可靠的生物标志物用于患者分层，并探索增强治疗效果同时最小化不良反应的联合疗法。通过将线粒体功能障碍作为MPN的潜在驱动因素来解决，这些新出现的方法有可能改善疾病管理、延长患者生存期并提高生活质量。此外，这种精准医学的新方法允许患者分层，并确保根据每个患者的个体疾病生物学制定治疗方案，从而总体上产生更好的结果。
