Amir Mohd, Javed Saleem
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India.
Front Genet. 2021 Oct 22;12:742802. doi: 10.3389/fgene.2021.742802. eCollection 2021.
Chronic myeloid leukemia is a malignancy of bone marrow that affects white blood cells. There is strong evidence that disease progression, treatment responses, and overall clinical outcomes of CML patients are influenced by the accumulation of other genetic and epigenetic abnormalities, rather than only the BCR/ABL1 oncoprotein. Both genetic and epigenetic factors influence the efficacy of CML treatment strategies. Targeted medicines known as tyrosine-kinase inhibitors have dramatically improved long-term survival rates in CML patients during the previous 2 decades. When compared to earlier chemotherapy treatments, these drugs have revolutionized CML treatment and allowed most people to live longer lives. Although epigenetic inhibitors' activity is disrupted in many cancers, including CML, but when combined with TKI, they may offer potential therapeutic strategies for the treatment of CML cells. The epigenetics of tyrosine kinase inhibitors and resistance to them is being studied, with a particular focus on imatinib, which is used to treat CML. In addition, the use of epigenetic drugs in conjunction with TKIs has been discussed. Resistance to TKIs is still a problem in curing the disease, necessitating the development of new therapies. This study focused on epigenetic pathways involved in CML pathogenesis and tumor cell resistance to TKIs, both of which contribute to leukemic clone breakout and proliferation.
慢性髓性白血病是一种影响白细胞的骨髓恶性肿瘤。有强有力的证据表明,慢性粒细胞白血病患者的疾病进展、治疗反应和总体临床结果受其他遗传和表观遗传异常积累的影响,而非仅受BCR/ABL1癌蛋白的影响。遗传和表观遗传因素均影响慢性粒细胞白血病治疗策略的疗效。在过去20年中,称为酪氨酸激酶抑制剂的靶向药物显著提高了慢性粒细胞白血病患者的长期生存率。与早期化疗相比,这些药物彻底改变了慢性粒细胞白血病的治疗方式,使大多数患者能够延长寿命。尽管表观遗传抑制剂的活性在包括慢性粒细胞白血病在内的许多癌症中受到破坏,但与酪氨酸激酶抑制剂联合使用时,它们可能为治疗慢性粒细胞白血病细胞提供潜在的治疗策略。正在研究酪氨酸激酶抑制剂的表观遗传学及其耐药性,尤其关注用于治疗慢性粒细胞白血病的伊马替尼。此外,还讨论了表观遗传药物与酪氨酸激酶抑制剂联合使用的情况。对酪氨酸激酶抑制剂的耐药性仍然是治愈该疾病的一个问题,因此需要开发新的治疗方法。本研究聚焦于慢性粒细胞白血病发病机制和肿瘤细胞对酪氨酸激酶抑制剂耐药性中涉及的表观遗传途径,这两者均促成白血病克隆的突破和增殖。