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Inhibition of c-REL using siRNA increased apoptosis and decreased proliferation in pre-B ALL blasts: Therapeutic implications
Source: Leukemia Research - August 26, 2017 Category: Hematology Authors: Seyedeh Momeneh Mohammadi, Daryosh Mohammadnejad, Abbas Ali Hosseinpour Feizi, Ali Akbar Movassaghpour, Soheila Montazer Saheb, Hojjatollah Nozad Charoudeh Tags: Original Article Source Type: research

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

Arsenic trioxide induces apoptosis in B-cell chronic lymphocytic leukemic cells through down-regulation of survivin via the p53-dependent signaling pathway
Abstract: Arsenic trioxide (As2O3) can induce apoptosis in many tumors. However, the associated mechanisms are not clearly understood. We found that As2O3 significantly inhibited the proliferation of WSU-CLL cells and induced apoptosis in dose- and time-dependent manners. WSU-CLL cells treated with 2μM As2O3 showed survivin down-regulation and p53 up-regulation. Survivin siRNA combined with As2O3 further inhibited the proliferation of WSU-CLL cells. p53 inhibition by siRNA prevented the down-regulation of survivin by As2O3 and prevented the As2O3-induced cytotoxicity of WSU-CLL cells. These results suggest that As2O3 may ...
Source: Leukemia Research - November 11, 2013 Category: Hematology Authors: Xiao-Hui Zhang, Ru Feng, Meng Lv, Qian Jiang, Hong-Hu Zhu, Ya-Zhen Qing, Jia-Ling Bao, Xiao-Jun Huang, X. Long Zheng 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

The role of TC-PTP (PTPN2) in modulating sensitivity to imatinib and interferon-α in CML cell line, KT-1 cells
Abstract: T-cell protein tyrosine phosphatase (TC-PTP, also known as PTPN2) is a negative regulator of the JAK/STAT pathway. STAT5 is activated by BCR-ABL kinase and STAT1 is an important transcription factor for interferon (IFN)-α-induced signaling in chronic myeloid leukemia (CML). We used siRNA to delete TC-PTP in the CML cell line, KT-1, and examined changes in the sensitivity to imatinib and IFN-α. Suppression of TC-PTP induced activation of STAT5, leading to imatinib resistance, while prolonged phosphorylation of STAT1 was induced by IFN-α, triggering cell death in KT-1 cells. These findings suggest that TC-PTP mo...
Source: Leukemia Research - June 6, 2013 Category: Hematology Authors: Yuriko Nishiyama-Fujita, Takatsune Shimizu, Morihiko Sagawa, Hideo Uchida, Masahiro Kizaki Tags: Laboratory Studies Source Type: research

Ectodomain shedding of CD200 from the B-CLL cell surface is regulated by ADAM28 expression
Abstract: CD200, a membrane glycoprotein of the immunoglobulin superfamily, is overexpressed in CLL. Soluble in serum CD200 (sCD200) is correlated with poor prognosis in CLL.ADAM (a disintegrin and metalloproteinase) enzymes are implicated in membrane protein shedding. ADAM28 mRNA expression in CLL was correlated with plasma sCD200 levels, and release into culture from CLL cells. siRNA for ADAM28 decreased release of sCD200 from cultures and transfection of a cloned ADAM28 gene into CD200+ cells enhanced release of sCD200.Our data support the hypothesis that ADAM28 plays a role in the shedding of CD200 from B-cell CLL cells.
Source: Leukemia Research - May 3, 2013 Category: Hematology Authors: Tal Twito, Zhiqi Chen, Ismat Khatri, Karrie Wong, David Spaner, Reg Gorczynski Tags: Laboratory 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

Imatinib and Nilotinib inhibit Bcr–Abl-induced ROS through targeted degradation of the NADPH oxidase subunit p22phox
In this study, using the K562 CML cell line we showed that inhibition of Bcr–Abl signalling, by either Imatinib or Nilotinib, led to a significant reduction in ROS levels which was concurrent with the GSK-3β dependent, post-translational down-regulation of the small membrane-bound protein p22phox, an essential component of the Nox complex. Furthermore, siRNA knockdown of p22phox in these cells established its importance in ROS production and proliferation. Taken together we believe our results provide a possible link between Bcr–Abl signalling and ROS production through Nox activity and demonstrate a novel mechanism o...
Source: Leukemia Research - December 5, 2012 Category: Hematology Authors: William D. Landry, John F. Woolley, Thomas G. Cotter Tags: Laboratory Studies Source Type: research