AUTHOR=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 

TITLE=Chemoresponse of de novo Acute Myeloid Leukemia to “7+3” Induction can Be Predicted by c-Myc-facilitated Cytogenetics

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.649267

DOI=10.3389/fphar.2021.649267

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Identifying patients with <italic>de novo</italic> 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 <italic>de novo</italic> AML.</p><p><bold>Methods:</bold> We stratified 75 untreated patients (24 and 51 from prospective and retrospective cohorts, respectively) with <italic>de novo</italic> 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 &gt; 40% of bone marrow myeloblasts being c-Myc (+).</p><p><bold>Results:</bold> 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; <italic>p</italic> = 0.047). Expression of the Myc gene and c-Myc protein were positively correlated (r = 0.495; <italic>p</italic> = 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%; <italic>p</italic> = 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%.</p><p><bold>Conclusion:</bold> The “7 + 3” induction remains the standard of care for <italic>de novo</italic> 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.</p>