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Total 71 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
Blockade of Ubiquitin Receptor PSMD4/Rpn10 Triggers Cytotoxicity and Overcomes Bortezomib-Resistance in Multiple Myeloma
ConclusionOur preclinical data validates targeting 19S proteasome ubiquitin receptor Rpn10 upstream of the proteasome in the ubiquitin proteasomal cascade, and provides the framework for clinical evaluation of Rpn10 inhibitors to overcome PI resistance and improve patient outcome in MM.DisclosuresAnderson: C4 Therapeutics: Equity Ownership, Other: Scientific founder; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; Millennium Takeda: Consultancy; OncoPep: Equity Ownership, Other: Scientific founder.
Source: Blood - November 21, 2018 Category: Hematology Authors: Song, Y., Ray, A., Chauhan, D., Anderson, K. Tags: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster II 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
Development of Liver-Specific Thrombopoietin Targeted Sirnas: Impact on Platelet Count, Megakaryocyte Mass, and Hematopoietic Progenitors in Normal and MPN Murine Models
The Thrombopoietin (THPO)/ thrombopoietin receptor (MPL) signaling axis is not only critical for the generation of platelets and megakaryocytes, but also for the maintenance of hematopoietic stem cells (HSC) and the bone marrow niche. MPL is expressed on primitive HSC, HSC progenitors, megakaryocytes, platelets, osteoblasts and osteoclasts, clonal hematopoietic stem cells and many leukemias. THPO production is constitutive but is also increased by inflammatory cytokines. Sustained exposure to high levels of THPO not only enhances platelet production, but also has a profound effect on HSC and the bone marrow microenvironmen...
Source: Blood - November 21, 2018 Category: Hematology Authors: Desai, D., Borodovsky, A., Davis, W. P., Degaonkar, R., Yucius, K., D'Angelo, K., Gedman, P., Williams, D. M., Rogers, O., Zhao, Z. J., Spivak, J. L., Moliterno, A. R. Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster III Source Type: research
Exosomes Derived from Cancer Associated Fibroblasts Elicit Survival and Drug Resistance of Primary Lymphoma Cells
ConclusionOur results suggest that CAFs and exosomes secreted from them are involved in the survival and drug resistance of patient lymphoma cells and play a pivotal role in the microenvironment of non-Hodgkin lymphoma. Exosomes would be a novel attractive therapeutic target.DisclosuresKiyoi: Sanofi K.K.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Celgene Corporation: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; FUJIFILM Corporation: Research Funding; Chuga...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kunou, S., Shimada, K., Hikita, T., Aoki, T., Sakamoto, A., Hayakawa, F., Oneyama, C., Kiyoi, H. Tags: 622. Lymphoma Biology-Non-Genetic Studies: Poster III Source Type: research
The Abnormal Expression and Mutation of Recombination Signal Binding Protein-Jk Gene Mightbe Contribute to the Proliferation of CD59- Clone in Paroxysmal Nocturnal Hemoglobinuria Patients
Conclusion: High expressed RBPJ was associated with hemolysis index in PNH, and inhibiting it can induced the apoptosis of PNH primary cells in vitro, indicating RBPJ may be involved in the proliferation of PNH clones.Figure.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Fu, R., LI, L., Liu, Z., Liu, H., Wang, H., Chen, Y., Shao, Z. Tags: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III 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
PIG-a Gene Expression Deficiency Association with Reduced DNA Damage Checkpoint Response and Activation
Conclusion:The above-mentioned results showed that there were decreased expressions of both DNA damage response checkpoint genes and repair genes in both the PIG-A CRISPR knockout leukemia cell lines as well as in the PNH patients. PIG-A mutation is globally associated with reduced DNA damage response capability and increased cellular stability. Our finding explains, at least partially, why PIG-A gene mutation status could be seen as a biomarker of mutagenesis and how PNH cells dominantly expend via clonal escape.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Pu, J. J., Lu, S., Nemesure, M., Teye, E. K., Schleicher, E., Moldovan, G.-L., Brodsky, R. A., Chen, F. Tags: 508. Bone Marrow Failure: 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
Endogenous STAT3-Activated Wnt5a Provides CLL Cells with Survival Advantage
In conclusion: STAT3 induces the expression of both ROR1 and its ligand Wnt5a. In that way STAT3 activates a micoenvironment-independent pro-survival pathway in CLL cells.DisclosuresBose: Incyte Corporation: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Constellation Pharmaceuticals: Research Funding; Pfizer, Inc.: Research Funding; CTI BioPharma: Research Funding; Blueprint Medicines Corporation: Research Funding. Thompson: Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Honoraria, Membe...
Source: Blood - November 21, 2018 Category: Hematology Authors: Rozovski, U., Li, P., Harris, D. M., Liu, Z., Jain, P., Ferrajoli, A., Burger, J. A., Bose, P., Thompson, P. A., Jain, N., Wierda, W. G., Keating, M. J., Estrov, Z. E. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research
Wnt5a Induces ROR1 Dependent Tyrosine Phosphorylation of DOCK2, and Enhanced Activation of ERK to Promote Proliferation of CLL Cells
We examined whether the proline-rich-domain (PRD) of ROR1, and SH3-binding motifs with the PRD that were necessary for these effects. We found that PRD and more specifically proline at 808 position of ROR1 was required to enhance phosphorylation of DOCK2 and activation of ERK1/2 over that seen in MEC1 cells lacking ROR1. We also found that inhibition of Rac using a small molecule inhibitor of Rac1/2 could suppress the capacity of Wnt5a to induce activation of ERK, suggesting that Wnt5a induced activation of Rac was required for activation of ERK. Finally, Wnt5a could not enhance the proliferation of CLL cells when treated ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kipps, T., Rassenti, L. Z., Widhopf II, G. F., Kipps, T. J. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research
Hemoglobin S Induces Exposure of Red Blood Cell Membrane Skeleton Microdomains Bearing Mannose That Stimulate Phagocytosis By Macrophages: A Molecular Basis for Hemolysis in Sickle Cell Disease but Protection Against Plasmodium Falciparum malaria
Heterozygosity for Hemoglobin (Hb) S, sickle cell trait (SCT), affects over 40 million people and confers resistance to severe infection by Plasmodium falciparum. Homozygosity for HbS, or compound heterozygosity with certain other alleles of Hb, affects over 4 million individuals and causes sickle cell disease (SCD). Hemolytic anaemia is a prominent feature of SCD and is mainly extravascular, mediated by hepatic and splenic macrophages. No ligands for this process have been identified. As many macrophage phagocytic receptors recognise carbohydrates, we surveyed surface glycan expression by sickle cells using a panel of 8 l...
Source: Blood - November 21, 2018 Category: Hematology Authors: Cao, H., Wassall, H. J., Forrester, M. A., Hall, L. S., Wilson, H. M., Shepherd, J., Patel, B., Masson, A., Henderson, S., Konieczny, G., Beverly, M., Tampakis, D., Antonopoulos, A., Haslam, S. M., Dell, A., Rowe, A. J., Brewin, J., Rees, D. C., Barker, R Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster III Source Type: research
FoxM1-Mediated Signaling Promotes the Progression of Mantle Cell Lymphoma
ConclusionWe have shown that FoxM1 inhibition may be a potential candidate treatment for MCL based on the results of our clinicopathological assessment and in vivo studies. Therefore, exploring the role of FoxM1 in MCL disease progression and therapeutic resistance may lead to novel therapeutic breakthroughs to improve patient clinical outcomes.DisclosuresWang: MoreHealth: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Research Funding; Kite Pharma: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Guo, H., Yao, Y., Zhang, H., Lorence, E., Ahmed, M., Ping, L., Nomie, K., Zhang, L., Wang, M. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Poster III Source Type: research
FOXM1 and the NPM-ALK/STAT3 Axis Form a Novel Positive Feedback Loop in Promoting the Oncogenesis of ALK-Positive Anaplastic Large Cell Lymphoma
Conclusions:In conclusion, we have identified a novel oncogenic feedback loop involving FOXM1 and the NPM-ALK/STAT3 axis in ALK+ALCL. This study has revealed the first clear example in which NPM-ALK exerts important oncogenic functions in the nuclei of ALK+ALCL cells, by means of its binding to an oncogenic transcription factor so as to promote its DNA binding and transcription activity.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Wang, P., Haque, M., Li, J., Huang, Y.-H., Almowaled, M., Bargar, C., Karpf, A., Chen, W., Turner, S., Lai, R. Tags: 603. Oncogenes and Tumor Suppressors: Poster III Source Type: research
