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Cancer: Acute Leukemia

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Total 260 results found since Jan 2013.

Loss of KDM6A Confers Drug Resistance in Acute Myeloid Leukemia
In conclusion, our results show that mutations in KDM6A are associated with the outgrowth of drug-resistant clones and highlight KDM6A as a novel biomarker of drug resistance in AML.DisclosuresHiddemann: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding. Metzeler: Novart...
Source: Blood - November 21, 2018 Category: Hematology Authors: Stief, S. M., Hanneforth, A.-L., Mattes, R., Weser, S., Vick, B., Bartoschek, M. D., Dominguez Moreno, H., Liu, W.-H., Ksienzyk, B., Rothenberg-Thurley, M., Quentmeier, H., Hiddemann, W., Metzeler, K. H., Schotta, G., Bultmann, S., Jeremias, I., Leonhardt Tags: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster III Source Type: research

Akt2 Mediates Glucocorticoid Resistance in Acute Lymphoblastic Leukemia through FoxO3a/Bim Axis and Serves As a Direct Target for Resistance Reversal
Conclusions: Akt2 might serve as a more direct and specific kinase mediating GC resistance through FoxO3a/Bim-signaling pathway in ALL, and targeting Akt2 with CCT128930 may be explored as a promising therapeutic strategy for resistance reversal.Figure.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Xie, M., Xie, Y., Yang, A., Ma, J., Wu, M., Jin, Y. Tags: 605. Molecular Pharmacology, Drug Resistance-Lymphoid and Other Diseases: Poster III Source Type: research

Targeted Delivery of CpG-Mir-146a Mimic Oligonucleotides As a Therapeutic Strategy to Reduce NF-Kb-Mediated Pathogenic Inflammation and Myeloid Leukemia Progression
NF-kB signaling plays central role in the regulation of immune cell activity. The microRNA-146a-5p (miR-146a) provides negative feedback inhibition of the NF-kB pathway to prevent either excessive immunity, such as cytokine release syndrome. Low expression of miR-146a is also implicated in certain types of leukemia, especially in del(5q)-syndrome myelodysplastic and acute myeloid leukemia (MDS/AML). While miR-146a is a potential therapeutic target, the lack of efficient miRNA delivery methods limits clinical translation. We previously developed a strategy for targeted delivery of oligonucleotide therapeutics, such as siRNA...
Source: Blood - November 21, 2018 Category: Hematology Authors: SU, Y.-L., Zhang, Z., Mann, M., Wang, X., Nguyen, L. X. T., Zhang, B., Li, L., Swiderski, P., Boldin, M., Forman, S. J., Marcucci, G., Kortylewski, M. Tags: 802. Chemical Biology and Experimental Therapeutics: Poster II Source Type: research

Ubiquitin-Activating Enzyme E1 Inhibition Caused Acute Leukemia Cell Apoptosis By Affecting CHOP Pathway
Conclusion: The inhibition of UBE1 activity can induce AML cell apoptosis by endoplasmic reticulum stress CHOP pathway. It will provide new clues for the treatment of acute myeloid leukemia.Disclosures: No relevant conflicts of interest to declare.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Bai, J., He, A., Wang, J., Yang, Y., Shen, Y., Feng, Y., Xu, Y. Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster II Source Type: research

Functional Analysis of CD99 Upregulation in Acute Myeloid Leukemia
Conclusion: In summary, our results suggests that even though CD99 enhances AML cell proliferation, it also enhances homotypic cell interaction and cell aggregation, which results in increased cell apoptosis as well as a decrease in cell migration and possibly responsible for the decrease leukemia engraftment. Further investigations are ongoing to determine the effect of homotypic interaction of CD99 in AML.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Vaikari, V. P., Yang, J., Akhtari, M., Alachkar, H. Tags: 603. Oncogenes and Tumor Suppressors Source Type: research

Topoisomerase I-DNA Covalent Complexes in Myeloid Malignancies: A Potential Biomarker for Topoisomerase I Inhibitor Sensitivity
Conclusions: Based on recent clinical results, there has been renewed interested in topoisomerase I inhibitors, especially for aggressive and transformed MPNs. Topoisomerase I-DNA complex repair/downregulation has been a hallmark of drug resistance to topoisomerase I inhibitors. Therefore, detecting and quantifying these complexes in treated samples has been hypothesized to provide insight into the drug sensitivity, which is particularly important in camptothecins and platinating agents given their narrow therapeutic windows. Immunodetection techniques using an anti-TopIcc antibody may help predict sensitivity of AML to to...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kohorst, M. A., Flatten, K. S., Peterson, K. L., Schneider, P. A., Correia, C., Pratz, K. W., Smith, B. D., Kaufmann, S. H. Tags: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases Source Type: research

The Novel Tumor Suppressor SAMHD1 Is Differentially Expressed and Partly Regulated By MYC in Peripheral T-Cell Lymphomas (PTCL)
Conclusions: SAMHD1 is shown for the first time to be differentially expressed among PTCL types and its regulation may involve MYC. Preliminary survival analysis shows no significant associations of SAMHD1 expression with EFS and OS in this cohort of PTCL, however, analysis of a larger PTCL study group is underway to draw definite conclusions.DisclosuresÖsterborg: Gilead: Consultancy, Research Funding; Beigene: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Abbvie: Research Funding.
Source: Blood - November 21, 2018 Category: Hematology Authors: Farrajota Neves Da Silva, P., Tsesmetzis, N., Xagoraris, I., Wasik, A. M., Kokaraki, G., Tzoras, E., Osterborg, A., Sander, B., Herold, N., Rassidakis, G. Tags: 622. Lymphoma Biology-Non-Genetic Studies: Poster III Source Type: research

SAMHD1 Is Variably Expressed in Mantle Cell Lymphoma and Correlated to SOX11 but Not to Survival
ConclusionsIn MCL the expression of SAMHD1 varies over a broad range and correlates to expression of SOX11. However, no significant difference in PFS or OS among patients receiving Ara-C containing induction chemotherapy is found in this study.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Wasik, A. M., Marin, E., Merrien, M., de Matos Rodrigues, J., Lord, M., Xagoraris, I., Christensson, B., Rassidakis, G., Jerkeman, M., Ek, S., Sander, B. Tags: 622. Lymphoma Biology-Non-Genetic Studies: Poster III Source Type: research

Genome-wide association analysis identifies SNPs predictive of in vitro leukemic cell sensitivity to cytarabine in pediatric AML.
Authors: Bargal SA, Rafiee R, Crews KR, Wu H, Cao X, Rubnitz JE, Ribeiro RC, Downing JR, Pounds SB, Lamba JK Abstract Cytarabine has been an integral part of acute myeloid leukemia (AML) chemotherapy for over four decades. However, development of resistance and high rates of relapse is a significant impediment in successfully treating AML. We performed a genome-wide association analysis (GWAS) and identified 113 (83 after adjusting for Linkage Disequilibrium) SNPs associated with in vitro cytarabine chemosensitivity of diagnostic leukemic cells from a cohort of 50 pediatric AML patients (p<10-4). Further evaluat...
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

DIXDC1 promotes the growth of acute myeloid leukemia cells by upregulating the Wnt/β-catenin signaling pathway
In this study, we aimed to investigate the expression status and potential biological function of DIXDC1 in AML. Our results showed that DIXDC1 expression was highly upregulated in AML cell lines and primary AML blasts compared with normal blasts. Knockdown of DIXDC1 by siRNA-mediated gene silencing significantly inhibited proliferation, induced cell cycle arrest, and promoted apoptosis of AML cells in vitro. By contrast, DIXDC1 overexpression promoted proliferation, accelerated cell cycle progression, and reduced apoptosis of AML cells. Moreover, we found that DIXDC1 knockdown decreased the expression of β-catenin and re...
Source: Biomedicine and Pharmacotherapy - September 19, 2018 Category: Drugs & Pharmacology Source Type: research

Scavenger Receptor Class BI (SR-BI) Mediates Uptake of CPX-351 into a K562 Leukemia Cells.
CONCLUSIONS: These preliminary studies suggest that SR-BI may be one potential mechanism by which CPX-351 is taken up into K562 cells. PMID: 30113235 [PubMed - as supplied by publisher]
Source: Drug Development and Industrial Pharmacy - August 18, 2018 Category: Drugs & Pharmacology Tags: Drug Dev Ind Pharm Source Type: research

Targeted Delivery of miR-146a Mimic Oligonucleotides as a Potential Therapeutic Approach to Modulate NF-kB Signaling in Myeloid Leukemia and Myeloproliferative Diseases
NF-kB signaling plays central role regulating cancer cell survival and self-renewal as well as immune cell activity. The microRNA-146a provides negative feedback inhibition of the NF-kB pathway and has been implicated in autoimmune diseases, such as graft versus host disease (GVHD), and in acute myeloid leukemia (AML). While it is a potential therapeutic target, the lack of efficient delivery of miRNA remains a challenge limiting clinical translation. We previously developed a strategy for targeted delivery of oligonucleotide therapeutics, such as siRNA, into human and mouse myeloid cells and B cells, using partly or compl...
Source: Experimental Hematology - August 1, 2018 Category: Hematology Authors: Yu-lin Su, Zhuoran Zhang, Piotr Swiderski, Defu Zeng, Guido Marcucci, Mark Boldin, Marcin Kortylewski Source Type: research

MiR-143 regulates proliferation and apoptosis of myelocytic leukemia cell HL-60 via modulating ERK1.
CONCLUSIONS: MiR-143 down-regulation and ERK1 up-regulation are correlated with APL pathogenesis. Their expression level affected patient's prognosis. MiR-143 targeted and inhibited ERK1 expression, weakened proliferation potency of HL-60 cells, and induced apoptosis. PMID: 29917183 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - June 20, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Deubiquitinase USP48 promotes ATRA-induced granulocytic differentiation of acute promyelocytic leukemia cells.
In conclusion, the present study highlights the function of USP48 in the ATRA-induced granulocytic differentiation of APL cells and provides a theoretical basis for identifying novel targets for differentiation therapy of APL. PMID: 29901102 [PubMed - as supplied by publisher]
Source: International Journal of Oncology - June 13, 2018 Category: Cancer & Oncology Authors: Li L, Wang Y, Zhang X, Song G, Guo Q, Zhang Z, Diao Y, Yin H, Liu H, Jiang G Tags: Int J Oncol Source Type: research

MYB induces the expression of the oncogenic corepressor SKI in acute myeloid leukemia.
Authors: Frech M, Teichler S, Feld C, Bouchard C, Berberich H, Sorg K, Mernberger M, Bullinger L, Bauer UM, Neubauer A Abstract Acute myeloid leukemia (AML) arises through clonal expansion of transformed myeloid progenitor cells. The SKI proto-oncogene is highly upregulated in different solid tumors and leukemic cells, but little is known about its transcriptional regulation during leukemogenesis. MYB is an important hematopoietic transcription factor involved in proliferation as well as differentiation and upregulated in most human acute leukemias. Here, we find that MYB protein binds within the regulatory region ...
Source: Oncotarget - June 4, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research