| Autor: |
Han Wang, Kathy Yuen Yee Chan, Chi Keung Cheng, Margaret H.L. Ng, Po Yi Lee, Frankie Wai Tsoi Cheng, Grace Kee See Lam, Tin Wai Chow, Shau Yin Ha, Alan K.S. Chiang, Wing Hang Leung, Anskar Y.H. Leung, Chi Chiu Wang, Tao Zhang, Xiao-Bing Zhang, Chi Chiu So, Yuet Ping Yuen, Qiwei Sun, Chi Zhang, Yaqun Xu, John Tak Kit Cheung, Wing Hei Ng, Patrick Ming-Kuen Tang, Wei Kang, Ka-Fai To, Wayne Yuk Wai Lee, Raymond S.M. Wong, Ellen Ngar Yun Poon, Qi Zhao, Junbin Huang, Chun Chen, Patrick Man Pan Yuen, Chi-kong Li, Alex Wing Kwan Leung, Kam Tong Leung |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Blood cancer discovery. 3(6) |
| ISSN: |
2643-3249 |
| Popis: |
Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacologic profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing candidates of immediate clinical relevance. Drug responses ex vivo correlated with patient characteristics, exhibited age-specific alterations, and concorded with activities in xenograft models. Integration with genomic data uncovered new gene–drug associations, suggesting actionable therapeutic vulnerabilities. Transcriptome profiling further identified gene-expression signatures associated with on- and off-target drug responses. We also demonstrated the feasibility of drug screening–guided treatment for children with high-risk AML, with two evaluable cases achieving remission. Collectively, this study offers a high-dimensional gene–drug clinical data set that could be leveraged to research the unique biology of pediatric AML and sets the stage for realizing functional precision medicine for the clinical management of the disease. Significance: We conducted integrated drug and genomic profiling of patient biopsies to build the functional genomic landscape of pediatric AML. Age-specific differences in drug response and new gene–drug interactions were identified. The feasibility of functional precision medicine–guided management of children with high-risk AML was successfully demonstrated in two evaluable clinical cases. This article is highlighted in the In This Issue feature, p. 476 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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