Guo Mengqi, He Yingzhi, Du Jingwen, Qiu Dezhi, Qin Yinjie, Huang Yuxian
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, P.R. China.
Recent Pat Anticancer Drug Discov. 2025 Jan 8. doi: 10.2174/0115748928330206241104161111.
BCL-2 was the first gene identified to have antiapoptotic effects, and venetoclax is an oral selective BCL-2 inhibitor, which has great potential in the treatment of patients with acute myeloid leukemia (AML) who are not candidates for intensive therapy. Notably, posaconazole, an oral antifungal drug, is also a strong factor that can affect blood venetoclax concentrations. To the best of our knowledge, the relationship between BCL-2 expression, posaconazole, and venetoclax, as well as their influence on treatment efficacy and the prognosis of patients with AML, has not been reported.
In this single-center retrospective study, the relationship between BCL-2 expression and blood venetoclax concentration was analyzed in 35 patients with AML. After that, we explored the differences in curative effect, adverse reactions, and outcomes between patients with different BCL-2 expression levels and patients with different venetoclax concentration levels, respectively.
BCL-2 mRNA expression levels were examined by reverse transcription quantitative PCR. Blood venetoclax concentrations were measured using high-performance liquid chromatography- tandem mass spectrometry.
The results revealed that among patients with AML, those with lower primary BCL-2 expression had a higher complete remission (CR) rate (p =0.005), overall response (OR) rate (p <0.0001), and progression-free survival time (p =0.04). Posaconazole was revealed to be a strong factor that was able to increase blood venetoclax concentration (p <0.001) and CR rate in the venetoclax plus posaconazole group compared to that in the venetoclax monotherapy group (p =0.002); however, no significant difference was identified in the occurrence of adverse reactions between these groups. Among low and high-blood venetoclax concentration groups, the event-free survival of the former group was significantly higher (p =0.013).
Higher levels of BCL-2 expression at initial diagnosis may have adverse effects on the efficacy and prognosis of patients, and higher levels of venetoclax concentration may advance the time of adverse reactions in patients, thus adversely affecting event-free survival (EFS).
BCL-2是首个被鉴定具有抗凋亡作用的基因，维奈克拉是一种口服选择性BCL-2抑制剂，在治疗不适合强化疗的急性髓系白血病（AML）患者方面具有巨大潜力。值得注意的是，口服抗真菌药物泊沙康唑也是一个会影响血液中维奈克拉浓度的重要因素。据我们所知，BCL-2表达、泊沙康唑和维奈克拉之间的关系，以及它们对AML患者治疗疗效和预后的影响尚未见报道。
在这项单中心回顾性研究中，分析了35例AML患者BCL-2表达与血液中维奈克拉浓度之间的关系。之后，我们分别探讨了不同BCL-2表达水平患者和不同维奈克拉浓度水平患者在疗效、不良反应及预后方面的差异。
采用逆转录定量PCR检测BCL-2 mRNA表达水平。使用高效液相色谱-串联质谱法测定血液中维奈克拉浓度。
结果显示，在AML患者中，初诊时BCL-2表达较低的患者完全缓解（CR）率更高（p =0.005）、总缓解（OR）率更高（p <0.0001）且无进展生存期更长（p =0.04）。与维奈克拉单药治疗组相比，泊沙康唑被证明是一个能够提高血液中维奈克拉浓度的重要因素（p <0.001），并且在维奈克拉联合泊沙康唑组中的CR率更高（p =0.002）；然而，这些组之间在不良反应发生率方面未发现显著差异。在血液中维奈克拉浓度低和高的组之间，前一组的无事件生存期显著更高（p =0.013）。
初诊时较高水平的BCL-2表达可能对患者的疗效和预后产生不利影响，而较高水平的维奈克拉浓度可能会使患者不良反应出现的时间提前，从而对无事件生存期（EFS）产生不利影响。
