Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns

BMC Cancer

Research Article

Helmut Rainer Salih¹  Kerstin Maria Kampa-Schittenhelm¹  Lothar Kanz¹  Olaf Salitzky¹  Figen Akmut¹  Marcus Matthias Schittenhelm¹  Barbara Illing¹ 

[1] University Hospital Tübingen, Dept. of Oncology, Hematology, Rheumatology, Immunology and Pulmology, Tübingen, Germany;

关键词: Delta9-Tetrahydrocannabinol;    Dronabinol;    THC;    Leukemia;    AML;    ALL;   

DOI  :  10.1186/s12885-015-2029-8

 received in 2015-04-14, accepted in 2015-12-17,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundIt has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity – however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia.MethodsTo test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo. Expression analysis for the CB1/2 receptors was performed by Western immunoblotting and flow cytometry. CB-receptor antagonists as well as a CRISPR double nickase knockdown approach were used to evaluate for receptor specificity of the observed proapoptotic effects.ResultsMeaningful antiproliferative as well as proapoptotic effects were demonstrated in a subset of cases – with a preference of leukemia cells from the lymphatic lineage or acute myeloid leukemia cells expressing lymphatic markers. Induction of apoptosis was mediated via CB1 as well as CB2, and expression of CB receptors was a prerequisite for therapy response in our models. Importantly, we demonstrate that antileukemic concentrations are achievable in vivo.ConclusionOur study provides rigorous data to support clinical evaluation of THC as a low-toxic therapy option in a well defined subset of acute leukemia patients.

【 授权许可】

CC BY   
© Kampa-Schittenhelm et al. 2016