RRC ID 57794
著者 Drenberg CD, Shelat A, Dang J, Cotton A, Orwick SJ, Li M, Jeon JY, Fu Q, Buelow DR, Pioso M, Hu S, Inaba H, Ribeiro RC, Rubnitz JE, Gruber TA, Guy RK, Baker SD.
タイトル A high-throughput screen indicates gemcitabine and JAK inhibitors may be useful for treating pediatric AML.
ジャーナル Nat Commun
Abstract Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates <40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.
巻・号 10(1)
ページ 2189
公開日 2019-5-16
DOI 10.1038/s41467-019-09917-0
PII 10.1038/s41467-019-09917-0
PMID 31097698
PMC PMC6522510
MeSH Adult Animals Antineoplastic Combined Chemotherapy Protocols / pharmacology* Antineoplastic Combined Chemotherapy Protocols / therapeutic use Bone Marrow / pathology Bone Marrow / radiation effects Bone Marrow Transplantation Cell Line, Tumor Child Child, Preschool Cytarabine / pharmacology Cytarabine / therapeutic use Deoxycytidine / analogs & derivatives* Deoxycytidine / pharmacology Deoxycytidine / therapeutic use Disease-Free Survival Female Gemcitabine High-Throughput Screening Assays / methods Humans Infant Janus Kinase Inhibitors / pharmacology* Janus Kinase Inhibitors / therapeutic use Leukemia, Experimental / drug therapy* Leukemia, Experimental / etiology Leukemia, Experimental / mortality Leukemia, Experimental / pathology Leukemia, Myeloid, Acute / drug therapy* Leukemia, Myeloid, Acute / mortality Leukemia, Myeloid, Acute / pathology Male Mice Mice, Inbred C57BL Mice, Transgenic Taxoids / pharmacology Taxoids / therapeutic use Whole-Body Irradiation / adverse effects Xenograft Model Antitumor Assays Young Adult
IF 12.121
引用数 3
リソース情報
ヒト・動物細胞 M-MOK(RCB2534)