Hsiao Tzu-Hung, Wang Ren Ching, Lu Tsai-Jung, Shih Chien-Hung, Su Yu-Chen, Tsai Jia-Rong, Jhan Pei-Pei, Lia Cai-Sian, Chuang Han-Ni, Chang Kuang-Hsi, Teng Chieh-Lin
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan.
Front Pharmacol. 2021 Apr 8;12:649267. doi: 10.3389/fphar.2021.649267. eCollection 2021.
Identifying patients with acute myeloid leukemia (AML) who will probably respond to the "7 + 3" induction regimen remains an unsolved clinical challenge. This study aimed to identify whether c-Myc could facilitate cytogenetics to predict a "7 + 3" induction chemoresponse in AML. We stratified 75 untreated patients (24 and 51 from prospective and retrospective cohorts, respectively) with AML who completed "7 + 3" induction into groups with and without complete remission (CR). We then compared Myc-associated molecular signatures between the groups in the prospective cohort after gene set enrichment analysis. The expression of c-Myc protein was assessed by immunohistochemical staining. We defined high c-Myc-immunopositivity as > 40% of bone marrow myeloblasts being c-Myc (+). Significantly more Myc gene expression was found in patients who did not achieve CR by "7 + 3" induction than those who did (2439.92 ± 1868.94 vs. 951.60 ± 780.68; = 0.047). Expression of the Myc gene and c-Myc protein were positively correlated (r = 0.495; = 0.014). Although the non-CR group did not express more c-Myc protein than the CR group (37.81 ± 25.13% vs. 29.04 ± 19.75%; = 0.151), c-Myc-immunopositivity could be a surrogate to predict the "7 + 3" induction chemoresponse (specificity: 81.63%). More importantly, c-Myc-immunopositivity facilitated cytogenetics to predict a "7 + 3" induction chemoresponse by increasing specificity from 91.30 to 95.92%. The "7 + 3" induction remains the standard of care for AML patients, especially for those without a high c-Myc-immunopositivity and high-risk cytogenetics. However, different regimens might be considered for patients with high c-Myc-immunopositivity or high-risk cytogenetics.
识别可能对“7 + 3”诱导方案有反应的急性髓系白血病（AML）患者仍然是一个尚未解决的临床挑战。本研究旨在确定c-Myc是否有助于通过细胞遗传学预测AML患者对“7 + 3”诱导化疗的反应。我们将75例完成“7 + 3”诱导治疗的未经治疗的AML患者（分别来自前瞻性队列和回顾性队列的24例和51例）分为完全缓解（CR）组和未完全缓解组。然后，在基因集富集分析后，我们比较了前瞻性队列中两组之间与Myc相关的分子特征。通过免疫组织化学染色评估c-Myc蛋白的表达。我们将高c-Myc免疫阳性定义为骨髓原始粒细胞中> 40%为c-Myc（+）。通过“7 + 3”诱导未达到CR的患者中发现的Myc基因表达明显高于达到CR的患者（2439.92±1868.94 vs. 951.60±780.68；P = 0.047）。Myc基因和c-Myc蛋白的表达呈正相关（r = 0.495；P = 0.014）。虽然未完全缓解组表达的c-Myc蛋白并不比完全缓解组多（37.81±25.13% vs. 29.04±19.75%；P = 0.151），但c-Myc免疫阳性可能是预测“7 + 3”诱导化疗反应的一个替代指标（特异性：81.63%）。更重要的是，c-Myc免疫阳性通过将特异性从91.30%提高到95.92%，有助于细胞遗传学预测“7 + 3”诱导化疗反应。“7 + 3”诱导仍然是AML患者的标准治疗方案，特别是对于那些没有高c-Myc免疫阳性和高危细胞遗传学的患者。然而，对于高c-Myc免疫阳性或高危细胞遗传学的患者，可能需要考虑不同的治疗方案。
