Sánchez-Sosa Santiago, Rodríguez-Medina Carlos, Stuckey Ruth, Florido Yanira, Santana Guillermo, González Martín Jesús María, Cruz-Cruz Naylén, Torres-Ochando Melissa, Fernández Rosa, Sánchez-Farías Nuria, Cionfrini Antonia, Labarta Teresa Molero, Gomez-Casares María Teresa, Bilbao-Sieyro Cristina
Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.
Medical Science Department, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
J Cancer. 2022 Feb 14;13(4):1356-1362. doi: 10.7150/jca.57457. eCollection 2022.
Recent advances in sequencing technologies and genomics have led to the development of several targeted therapies such as BCL2 and Bromodomain and extra-terminal (BET) protein inhibitors for a more personalized treatment of patients with acute myeloid leukemia (AML), yet the majority of patients still receive standard induction chemotherapy. The molecular profiles of patients who are likely to respond to induction therapy and novel directed therapies remain to be determined. The expression of AML-related genes that are targeted by novel therapies such as and , as well as functionally related genes and associated epigenetic modulators (, , , ) were analyzed in a series of 176 consecutive AML patients at multiple points during the disease course - diagnosis (Dx), post-induction (PI), complete remission (CR) and relapse (RL) - and their relationship with clinical variables and outcome investigated. Higher expression was observed PI and at CR compared to Dx, with significantly superior expression after induction therapy in the group of patients who reached CR compared to those who did not. Thus, the upregulation of at PI may be a marker of CR in AML patients. On the other hand, cells with high levels of and may be vulnerable to BRD4 inhibition.
测序技术和基因组学的最新进展已促成了几种靶向疗法的开发，如BCL2以及含溴结构域和额外末端（BET）蛋白抑制剂，用于对急性髓系白血病（AML）患者进行更个性化的治疗，但大多数患者仍接受标准诱导化疗。可能对诱导治疗和新型定向疗法有反应的患者的分子谱仍有待确定。在一系列176例连续的AML患者疾病过程中的多个时间点——诊断（Dx）、诱导后（PI）、完全缓解（CR）和复发（RL）——分析了诸如[具体基因1]和[具体基因2]等新型疗法所靶向的AML相关基因的表达，以及功能相关基因和相关表观遗传调节因子（[基因3]、[基因4]、[基因5]、[基因6]），并研究了它们与临床变量和结局的关系。与Dx相比，在PI期和CR期观察到[具体基因]表达更高，与未达到CR的患者组相比，在诱导治疗后达到CR的患者组中[具体基因]表达显著更高。因此，PI期[具体基因]的上调可能是AML患者CR的一个标志物。另一方面，具有高水平[具体基因1]和[具体基因2]的细胞可能对BRD4抑制敏感。
