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5 ′-triphosphate siRNA targeting MDR1 reverses multi-drug resistance and activates RIG-I-induced immune-stimulatory and apoptotic effects against human myeloid leukaemia cells
Most persons with acute myeloid leukaemia fail therapy. Development of multi-drug resistance (MDR) is thought to be an important cause. MDR is characterized by cross-resistance to several anti-cancer drugs with diverse chemical structures and mechanisms-of-action [1]. MDR involves the expression and activity of an ATP-binding-cassette (ABC; CD243) transporter also known as P-glycoprotein (P-gp), an efflux pump protein which extrudes anti-cancer drugs from cells [2]. Additionally, P-gp is associated with decreased caspase activation resulting from altered activity of several chloride channels [3,4] altered intra-cellular pH...
Source: Leukemia Research - March 19, 2017 Category: Hematology Authors: Dengzhe Li, Robert Peter Gale, Yanfeng Liu, Baoxia Lei, Yuan Wang, Dongmei Diao, Mei Zhang Tags: Research paper Source Type: research

Attenuated A20 expression of acute myeloid leukemia-derived dendritic cells increased the anti-leukemia immune response of autologous cytolytic T cells
In this study, A20 expression was up-regulated in AML-DCs activated with tumor necrosis factor (TNF)-α. Then, A20 attenuation with siRNA in AML-DC enhanced the expression of several co-stimulatory molecules and proinflammatory cytokines. Furthermore, after A20 attenuation in AML-DCs, the autologous cytolytic T cells (CTLs) induced by AML-DCs had higher killing capability and specificity for primary AML cells. Additionally, receptor-interacting protein (RIP) and the NF-κBp65 pathway were elevated in AML-DCs when A20 was reduced. Hence, this study identified A20 as a negative regulator for controlling AML-DC maturation and...
Source: Leukemia Research - April 7, 2014 Category: Hematology Authors: Xiaoying Zhang, Yongfeng Su, Haifeng Song, Zhiyong Yu, Bin Zhang, Hu Chen Tags: Clinical Studies Source Type: research

Distinct poor prognostic subgroups of acute myeloid leukaemia, FLT3-ITD and P-glycoprotein-positive, have contrasting levels of FOXO1
Abstract: Regulation of ABCB1 (P-glycoprotein/Pgp) in AML was investigated. In a historical cohort with Pgp and transcriptional regulator expression profiling data available (n=141), FOXO1 correlated with Pgp protein expression. This was confirmed in an independent cohort (n=204). Down-regulation (siRNA) or hyperactivation (nicotinamide) of FOXO1 led to corresponding changes in Pgp. Low FOXO1 expression correlated with FLT3-ITDs (p
Source: Leukemia Research - November 25, 2013 Category: Hematology Authors: Claire H. Seedhouse, Ken I. Mills, Sophie Ahluwalia, Martin Grundy, Shili Shang, Alan K. Burnett, Nigel H. Russell, Monica Pallis Tags: Laboratory Studies Source Type: research

The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia
In conclusion, our data point to HDAC4 as drug target in childhood ALL, especially in prednisone poor-responders.
Source: Leukemia Research - August 14, 2013 Category: Hematology Authors: Bernd Gruhn, Thomas Naumann, Dorothee Gruner, Mario Walther, Susan Wittig, Sabine Becker, James F. Beck, Jürgen Sonnemann Tags: Clinical Studies Source Type: research

Endogenous stromal cell-derived factor-1 (CXCL12) supports autonomous growth of acute myeloid leukemia cells
Abstract: We investigated the role of endogenous stromal cell-derived factor-1 (SDF-1; CXCL12) in the survival and proliferation of acute myeloid leukemia (AML) cells in vitro. CD34+ cells from the peripheral blood of five patients with AML, as well as five AML cell lines, produced and secreted SDF-1. Knock-down of endogenous SDF-1 expression using siRNA technology downregulated the constitutive phosphorylation of SDF-1-related signaling molecules and significantly inhibited spontaneous proliferation of the AML cell lines during a 3-day incubation in serum-free conditions. These results indicate that endogenous SDF-1 expre...
Source: Leukemia Research - March 7, 2013 Category: Hematology Authors: Ha-Yon Kim, Yoon-Suk Oh, Ik-Chan Song, Seong-Woo Kim, Hyo-Jin Lee, Hwan-Jung Yun, Samyong Kim, Deog-Yeon Jo Tags: Laboratory Studies Source Type: research