PDF(Pubmed)
Abstract：
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.
摘要：
慢性粒细胞白血病是骨髓的恶性肿瘤，会影响白细胞。有强有力的证据表明疾病进展，治疗反应，CML患者的总体临床结果受其他遗传和表观遗传异常的积累影响，而不仅仅是BCR/ABL1癌蛋白。遗传和表观遗传因素都会影响CML治疗策略的疗效。在过去的20年里，被称为酪氨酸激酶抑制剂的靶向药物显著提高了CML患者的长期生存率。与早期的化疗相比，这些药物彻底改变了CML治疗，并使大多数人的寿命更长。虽然表观遗传抑制剂的活性在许多癌症中被破坏，包括CML,但是当与TKI结合时，它们可能为CML细胞的治疗提供潜在的治疗策略.酪氨酸激酶抑制剂的表观遗传学及其抗性正在研究中，特别关注伊马替尼，用于治疗慢性粒细胞白血病。此外,已经讨论了表观遗传药物与TKIs的联合使用。对TKIs的抗性仍然是治疗这种疾病的一个问题，需要开发新的疗法。这项研究集中在CML发病机制和肿瘤细胞对TKIs的抗性中涉及的表观遗传途径。两者都有助于白血病克隆爆发和增殖。
