کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5527874 1547895 2017 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
CPX-351 exhibits potent and direct ex vivo cytotoxicity against AML blasts with enhanced efficacy for cells harboring the FLT3-ITD mutation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
CPX-351 exhibits potent and direct ex vivo cytotoxicity against AML blasts with enhanced efficacy for cells harboring the FLT3-ITD mutation
چکیده انگلیسی


- CPX-351 is a liposome formulation of cytarabine and daunorubicin in 5:1 molar ratio.
- CPX-351 has ex vivo activity against a broad range of hematologic malignancies.
- Consistent with clinical data, CPX-351 activity is retained in high-risk AML blasts.
- Ex vivo analysis of AML blasts with FLT3-ITD shows increased sensitivity to CPX-351.
- Ex vivo analysis identifies AML subgroups warranting further clinical investigation.

PurposeIdentify AML patients most likely to respond to CPX-351, a nano-scale liposome formulation containing cytarabine and daunorubicin co-encapsulated at a 5:1 molar ratio.MethodsWe examined the ex vivo cytotoxic activity of CPX-351 against leukemic cells isolated from 53 AML patients and an additional 127 samples including acute lymphoblastic leukemia, myelodysplastic syndrome/myeloproliferative neoplasms, or chronic lymphocytic leukemia/lymphoma. We assessed activity with respect to common molecular lesions and used flow cytometry to assess CPX-351 cellular uptake.ResultsAML specimen sensitivity to CPX-351 was similar across conventional risk groups. FLT3-ITD cases were five-fold more sensitive to CPX-351. CPX-351 was active across other indications with nearly all cases exhibiting IC50 values markedly lower than reported 72-h plasma drug concentration in patients receiving CPX-351. The range and distribution of CPX-351 IC50 values were comparable for AML, CLL, and ALL, whereas MDS/MPN cases were less sensitive. CPX-351 uptake analysis revealed a correlation between uptake of CPX-351 and cytotoxic potency.ConclusionsOur findings are consistent with clinical data, in which CPX-351 activity is retained in high-risk AML patients. Ex vivo analysis of cytotoxic potency may provide a means to identify specific AML subsets, such as FLT3-ITD, that benefit most from CPX-351 and warrant additional clinical evaluation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 53, February 2017, Pages 39-49
نویسندگان
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