Purpose-To investigate the molecular mechanism underlying intrinsic resistance to Experimental Design-Western blots and real-time RT-PCR were used to determine levels of Mcl-1 after Conclusions-Our results demonstrate that sequestration of Bim by Mcl-1 is a mechanism of intrinsic ABT-199 resistance and supports the clinical development of ABT-199 in combination with cytarabine or daunorubicin for the treatment of AML. HHS Public AccessAuthor manuscript Clin Cancer Res. Author manuscript; available in PMC 2017 September 01.

Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.

No abstract

Purpose: To investigate the efficacy of the combination of the FLT3 inhibitors midostaurin or gilteritinib with the Bcl-2 inhibitor venetoclax in FLT3-ITD acute myeloid leukemia (AML) and the underlying molecular mechanism. Experimental Design: Using both FLT3-ITD cell lines and primary patient samples, annexin V-FITC/propidium iodide staining and flow cytometry analysis were used to quantify cell death induced by midostaurin or gilteritinib, alone or in combination with venetoclax. Western blot analysis was performed to assess changes in protein expression levels of members of the JAK/ STAT, MAPK/ERK, and PI3K/AKT pathways, and members of the Bcl-2 family of proteins. The MV4-11-derived xenograft mouse model was used to assess in vivo efficacy of the combination of gilteritinib and venetoclax. Lentiviral overexpression of Mcl-1 was used to confirm its role in cell