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Cancer: Acute Leukemia

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Total 260 results found since Jan 2013.

CD22ΔE12 as a molecular target for RNAi therapy
Summary B‐precursor acute lymphoblastic leukaemia (BPL) is the most common form of cancer in children and adolescents. Our recent studies have demonstrated that CD22ΔE12 is a characteristic genetic defect of therapy‐refractory clones in paediatric BPL and implicated the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy‐refractory paediatric BPL. The purpose of the present study is to evaluate the biological significance of the CD22ΔE12 molecular lesion in BPL and determine if it could serve as a molecular target for RNA interference (RNAi) therapy. Here we report a previously unrecognized ca...
Source: British Journal of Haematology - February 6, 2015 Category: Hematology Authors: Fatih M. Uckun, Hong Ma, Jianjun Cheng, Dorothea E. Myers, Sanjive Qazi Tags: Research Paper Source Type: research

The antitumor compound triazoloacridinone C-1305 inhibits FLT3 kinase activity and potentiates apoptosis in mutant FLT3-ITD leukemia cells.
Conclusion:C-1305 induces apoptosis in FLT3-ITD-expressing human leukemia cells in vitro, suggesting that mutated FLT3 kinase can be a new target for C-1305, and C-1305 may be a drug candidate for the therapeutic intervention in FLT3-associated AML. PMID: 25640477 [PubMed - as supplied by publisher]
Source: Acta Pharmacologica Sinica - February 2, 2015 Category: Drugs & Pharmacology Authors: Augustin E, Skwarska A, Weryszko A, Pelikant I, Sankowska E, Borowa-Mazgaj B Tags: Acta Pharmacol Sin Source Type: research

Deguelin, a selective silencer of the NPM1 mutant, potentiates apoptosis and induces differentiation in AML cells carrying the NPM1 mutation
In conclusion, deguelin is a potent in vitro inhibitor of the mutant form of NPM1, which provides the molecular basis for its anti-leukemia activities in NPM1 mutant acute myeloid leukemia cells.
Source: Annals of Hematology - January 13, 2015 Category: Hematology Source Type: research

Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation.
Abstract Heme oxygenase-1 was reported previously as a resistance target on acute myelocytic leukemia (AML). We found that HO-1 was resistant to 5-azacytidine (AZA) treatment of myelodysplastic syndrome (MDS), and explored further the relative mechanisms. Patient bone marrow mononuclear cells (n=48) diagnosed as different levels of MDS were collected. Cell growth was evaluated by MTT assay; cell cycle and apoptosis were detected by flow cytometry; mRNA expression was assessed by real-time PCR, protein expression was analyzed through western blotting. Methylation was assessed by MSP. The survival time, and weight o...
Source: International Journal of Oncology - January 12, 2015 Category: Cancer & Oncology Authors: Wang P, Ma D, Wang J, Fang Q, Gao R, Wu W, Lu T, Cao L Tags: Int J Oncol Source Type: research

Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma.
Abstract Malignant pleural mesothelioma is a global health issue. Arsenic trioxide (ATO) has been shown to suppress thymidylate synthase (TYMS) in lung adenocarcinoma and colorectal cancer, and induce apoptosis in acute promyelocytic leukemia. With TYMS as a putative therapeutic target, the effect of ATO in mesothelioma was therefore studied. A panel of 5 mesothelioma cell lines was used to study the effect of ATO on cell viability, protein expression, mRNA expression and TYMS activity by MTT assay, western blot, qPCR and tritium-release assay, respectively. The knockdown of TYMS and E2F1 was performed with a spec...
Source: International Journal of Oncology - October 21, 2014 Category: Cancer & Oncology Authors: Lam SK, Li YY, Zheng CY, Ho JC Tags: Int J Oncol Source Type: research

Abstract 799: Diminishing Mcl-1 protein leads to apoptosis of acute myeloid leukemia cells responding to all trans retinoic acid differentiation
All trans retinoic acid (ATRA) is successfully used for the treatment of acute promyelocytic leukemia (APL) through inducing terminal differentiation and death receptor-mediated apoptosis. However, ATRA has limited clinic efficacy in non-APL acute myeloid leukemia (AML) patients. To extend ATRA therapy to AML (non-APL), cell death and differentiation induction were tested and compared in a panel of AML cell lines after treatment with ATRA for 2, 4 and 6 days based on the staining of CD11b and annexin V, respectively. ATRA treatment in APL NB4 cells induces differentiation but not apoptosis at 2 days. ATRA differentiation p...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Wang, R., Xia, L., Gabrilove, J., Waxman, S., Jing, Y. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 3964: NVP-BEZ235 enhances dexamethasone-induced BIM expression and apoptosis in models of T-ALL with PTEN dysfunction and increased PI3K/AKT activity
Introduction: Glucocorticoid (GC) resistance presents a major challenge in pediatric acute lymphoblastic leukemia (ALL) treatment. Increased activation of the PI3K/AKT pathway, which may occur following loss of PTEN function, may be a possible mechanism of GC resistance. We therefore investigated the effects of inhibiting the PI3K/AKT pathway with the dual PI3K/mTOR inhibitor NVP-BEZ235 on the enhancement of dexamethasone activity in in vitro and in vivo models of ALL and the role the PI3K/AKT pathway plays in resistance to GCs. Methods: Cytotoxicity of NVP-BEZ235, dexamethasone, and the combination were evaluated using DI...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Hall, C., Kang, M. Tags: Tumor Biology Source Type: research

Abstract 4233: Mef2C enhances 1,25-dihydroxyvitamin D3-induced monocytic differentiation of human myeloid leukemia cells by regulating C/EBP{beta} expression
Myogenic enhancer factors 2 (Mef2) are members of the family of MADS (MCM1-agamous-deficiens-serum response factor)-box transcription factors known to have multiple roles in morphogenesis of skeletal, cardiac and smooth muscle cells. Recently, Mef2C was found to be also involved in hematopoiesis. Bone marrow cells isolated from Mef2C knockout mice demonstrated decreased monocytic differentiation in response to cytokine stimulation, whereas constitutive expression of Mef2C promoted monopoiesis. The above findings led us to examine the role of Mef2C in 1,25-dihydroxyvitamin D3 (1,25D)-induced monocytic differentiation. Human...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Zheng, R., Wang, X., Studzinski, G. P. Tags: Molecular and Cellular Biology Source Type: research

Abstract 5248: Targeted suppression of interleukin-1 signaling inhibits growth of primary human acute myeloid leukemia cells
Conclusion: These results demonstrate a novel role for IL-1 signaling in promoting oncogenesis in AML and provide evidence that targeting this pathway might be beneficial to AML patients. Citation Format: Anupriya Agarwal, Alyssa Carey, Elie Traer, Jeffrey Tyner, Grover C. Bagby, Brian J. Druker. Targeted suppression of interleukin-1 signaling inhibits growth of primary human acute myeloid leukemia cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5248. doi:10.1158/1538-7445.AM2014-5248
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Agarwal, A., Carey, A., Traer, E., Tyner, J., Bagby, G. C., Druker, B. J. Tags: Molecular and Cellular Biology Source Type: research

Abstract 952: Preclinical efficacy of maternal embryonic leucine-zipper kinase (MELK) inhibition in acute myeloid leukemia
Maternal embryonic leucine-zipper kinase (MELK), a member of the serine-threonine kinases snf1/AMP-activated protein family is involved in mammalian embryonic development. MELK is aberrantly upregulated in several types of solid cancer including glioblastoma and breast cancer, and implicated in formation and maintenance of cancer stem cells. Little is known about the relevance of this kinase in hematological malignancies. Our study aimed to explore the role of MELK in acute myeloid leukemia (AML) and identify whether targeting this kinase in leukemia stem cells may have therapeutic relevance. In order to characterize the e...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Alachkar, H., Mutonga, M., Chung, S., Matsuo, Y., Stock, W., Nakamura, Y. Tags: Experimental and Molecular Therapeutics Source Type: research

Inhibition of long non-coding RNA NEAT1 impairs myeloid differentiation in acute promyelocytic leukemia cells
Conclusions: Our results indicate that reduced expression of the nuclear long noncoding RNA NEAT1 may play a role in the myeloid differentiation of APL cells.
Source: Epidemiologic Perspectives and Innovations - September 23, 2014 Category: Epidemiology Authors: Chengwu ZengYan XuLing XuXibao YuJingjing ChengLijian YangShaohua ChenYangqiu Li Source Type: research

Targeted therapy with MXD3 siRNA, anti‐CD22 antibody and nanoparticles for precursor B‐cell acute lymphoblastic leukaemia
In this study, we hypothesize that an effective siRNA therapy for preB ALL can be developed using antiCD22 antibody (αCD22 Ab) and nanoparticles. We composed nanocomplexes with super paramagnetic iron oxide nanoparticles (SPIO NPs), αCD22 Abs and MXD3 siRNA molecules based on physical interactions between the molecules. We demonstrated that the MXD3 siRNA‐αCD22 Ab‐SPIO NP complexes entered leukaemia cells and knocked down MXD3, leading the cells to undergo apoptosis and resulting in decreased live cell counts in the cell line Reh and in primary preB ALL samples in vitro. Furthermore, the cytotoxic effects of the MXD...
Source: British Journal of Haematology - September 8, 2014 Category: Hematology Authors: Noriko Satake, Connie Duong, Cathy Chen, Gustavo A. Barisone, Elva Diaz, Joseph Tuscano, David M. Rocke, Jan Nolta, Nitin Nitin Tags: Research Paper Source Type: research

Inactivation of FoxM1 transcription factor contributes to curcumin-induced inhibition of survival, angiogenesis, and chemosensitivity in acute myeloid leukemia cells.
In this study, we found that curcumin inhibited cell survival accompanied by induction of G2/M cell cycle arrest and apoptosis in HL60, Kasumi, NB4, and KG1 cells. This was associated with concomitant attenuation of FoxM1 and its downstream genes, such as cyclin B1, cyclin-dependent kinase (CDK) 2, S-phase kinase-associated protein 2, Cdc25B, survivin, Bcl-2, matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor (VEGF), as well as the reduction of the angiogenic effect of AML cells. We also found that specific downregulation of FoxM1 by siRNA prior to curcumin treatment resulted in enhanced cell s...
Source: Molecular Medicine - September 3, 2014 Category: Molecular Biology Authors: Zhang JR, Lu F, Lu T, Dong WH, Li P, Liu N, Ma DX, Ji CY Tags: J Mol Med (Berl) Source Type: research

Inactivation of FoxM1 transcription factor contributes to curcumin-induced inhibition of survival, angiogenesis, and chemosensitivity in acute myeloid leukemia cells
In this study, we found that curcumin inhibited cell survival accompanied by induction of G2/M cell cycle arrest and apoptosis in HL60, Kasumi, NB4, and KG1 cells. This was associated with concomitant attenuation of FoxM1 and its downstream genes, such as cyclin B1, cyclin-dependent kinase (CDK) 2, S-phase kinase-associated protein 2, Cdc25B, survivin, Bcl-2, matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor (VEGF), as well as the reduction of the angiogenic effect of AML cells. We also found that specific downregulation of FoxM1 by siRNA prior to curcumin treatment resulted in enhanced cell s...
Source: Journal of Molecular Medicine - September 3, 2014 Category: Molecular Biology Source Type: research

Involvement of C/EBPβ in monocytic differentiation of acute myeloid leukemia cells induced by LW-218, a new synthesized flavonoid.
In this study, we found that LW-218, a new synthesized flavonoid, inhibited proliferation and induced differentiation of acute myeloid leukemia cells. The IC50s of LW-218 in HL-60, U937, K562, and NB4 cell lines were all less than 5 μM, suggesting greater capacity than compounds we have reported. LW-218 induced differentiation effects including morphologic changes, NBT reduction, and both of CD11b and CD14 expression. Results of western blots and siRNA transfection revealed that LW-218 increased the LAP/LIP ratio of C/EBPβ which regulated monocytic differentiation of leukemia cells. Meanwhile, these differentiation eff...
Source: Neoplasma - August 23, 2014 Category: Cancer & Oncology Authors: Wang Q, Hui H, Yang H, Li H, Gao Y, Li Z, Guo Q, Lu N Tags: Neoplasma Source Type: research