Gls Inhibitor CB-839 Modulates Cellular Metabolism in AML and Potently Suppresses AML Cell Growth When Combined with 5-Azacitidine
نویسندگان
چکیده
منابع مشابه
Inhibiting glutaminase in acute myeloid leukemia: metabolic dependency of selected AML subtypes
Metabolic reprogramming has been described as a hallmark of transformed cancer cells. In this study, we examined the role of the glutamine (Gln) utilization pathway in acute myeloid leukemia (AML) cell lines and primary AML samples. Our results indicate that a subset of AML cell lines is sensitive to Gln deprivation. Glutaminase (GLS) is a mitochondrial enzyme that catalyzes the conversion of G...
متن کاملDual inhibition of Fes and Flt3 tyrosine kinases potently inhibits Flt3-ITD+ AML cell growth
Acute myelogenous leukemia (AML) is often associated with activating mutations in the receptor tyrosine kinase, Flt3, including internal tandem duplications (ITDs) within the regulatory juxtamembrane region. Previous studies have linked Flt3-ITD to the activation of the Fes protein tyrosine kinase in AML, and RNAi-knockdown studies suggest that Fes may be required for Flt3 function. In this stu...
متن کاملGlutaminolysis gets the spotlight in cancer
The fact that cancer cells rewire their metabolism to meet their extreme energetic and biosynthetic needs has long been known, since the seminal studies by Otto Warburg demonstrated that cancer cells heavily rely on glycolysis even in the presence of oxygen, the so-called Warburg effect. However, efforts to therapeutically target the special requirements of cancer cells have only gained tractio...
متن کاملAzacitidine combined with the selective FLT3 kinase inhibitor crenolanib disrupts stromal protection and inhibits expansion of residual leukemia-initiating cells in FLT3-ITD AML with concurrent epigenetic mutations
Effectively targeting leukemia-initiating cells (LIC) in FLT3-ITD-mutated acute myeloid leukemia (AML) is crucial for cure. Tyrosine kinase inhibitors (TKI) have limited impact as single agents, failing to eradicate LIC in the bone marrow. Using primary AML samples and a patient-derived xenograft model, we investigated whether combining the FLT3-selective TKI crenolanib with the hypomethylating...
متن کاملGlutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells
Curative responses in the treatment of multiple myeloma (MM) are limited by the emergence of therapeutic resistance. To address this problem, we set out to identify druggable mechanisms that convey resistance to proteasome inhibitors (PIs; e.g., bortezomib), which are cornerstone agents in the treatment of MM. In isogenic pairs of PI sensitive and resistant cells, we observed stark differences ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Blood
سال: 2016
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood.v128.22.4064.4064