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Total 11 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

Multiple Myeloma Cell-Derived Interleukin-32gamma Increases the Immunosuppressive Function of Macrophages By Promoting Indoleamine 2,3-Dioxygenase (IDO) Expression
Conclusion: Our study showed that MM cell-derived IL-32 induced IDO production in Ms through PR3 and the downstream STAT3 and NF-B pathways, resulting in the suppression of the proliferation and effector function of CD4+ T cells. High IL-32 expression in MM may contribute to an immunosuppressive microenvironment by upregulating IDO production in Ms and promote MM progression.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Yan, H., He, D., Huang, X., Fan, Z. E., Huang, H., Cai, Z. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II Source Type: research

CIC-Mutation As a Potential Molecular Mechanism of Acquired Resistance to Combined BRAF/MEK Inhibition in CNS Multiple Myeloma
Central nervous system (CNS) involvement is an extremely rare extramedullary multiple myeloma (MM) manifestation, diagnosed in less than 1% of patients. It is considered an ultimate high-risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases.In June 2017 an 81 years old male with a light chain MM was referred to our institution for an isolated CNS MM relapse. His cerebrospinal fluid (CSF) demonstrated a high load of clonal plasma cells, however, the patient's bone marrow infiltration was very little with a percentage of...
Source: Blood - November 21, 2018 Category: Hematology Authors: Da Via', M. C., Solimando, A. G., Garitano-Trojaola, A., Barrio, S., Rodhes, N., Strifler, S., Teufel, E., Lapa, C., Einsele, H., Beilhack, A., Kortum, K. M. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II Source Type: research

CD55 and CD59 Can Limit the Anti-Tumor Efficacy of Daratumumab in Natural Killer/T-Cell Lymphoma
In this report we show that subsequent testing in an NKTL mouse xenograft model confirms the potency of Daratumumab in vivo as evidenced by the inhibition in tumour progression and prolongation of mouse survival. When treatment was continued over a month, some tumors began to rapidly enlarge ('Resistant') while the rest remained similar or smaller ('Sensitive') than the tumour volume at the initiation of Daratumumab treatment. An mRNA analysis comparing 'Resistant' and 'Sensitive' tumors showed that while both tumours bore similar levels of CD38 expression, resistant tumours displayed an upregulation of complement inhibito...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mustafa, N., Nee, A. H. F., Chooi, J. Y., Toh, S. H. M., Hee, Y. T., Selvarajan, V., Zhou, L., Yang, J., Chng, W. J. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Poster I Source Type: research

The Role and Mechanism of Upregulation of HO-1 Expression By Activating of Adenosine-2a Receptor in the Tumor Immune Microenvironment with Diffuse Large B-Cell Lymphoma
Conclusion: It is essential for the maintenance and survival of tumor cells in the tumor immune microenvironment. Upregulation of HO-1 by A2aR receptor activation plays an important role in the immune microenvironment of DLBCL tumors.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Wang, C., Wang, J. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Poster II Source Type: research

Chidamide, a Novel Histone Deacetylase Inhibitor, Inhibits Multiple Myeloma Cells Proliferation through Succinate Dehydrogenase Subunit a
Most patients with multiple myeloma (MM) would finally relapse. Current chemotherapy regimens have limited effect on relapse MM patients. As a new histone deacetylase inhibitor, chidamide has been used in malignancy treatment such as peripheral T-cell lymphoma. However, it is still unknown if chidamide can be used in MM.To determine the target gene of chidamide in MM patients, we performed RNA-Seq analysis using 3 MM patients' bone marrow mononuclear cells. Their BMMCs were cultured with 6μM chidamide or not, and six of the most significantly changed coding genes were selected. Realtime RT-PCR showed that compared with ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Sun, Y., Liu, P., Li, J. Tags: 653. Myeloma: Therapy, excluding Transplantation: Poster I Source Type: research

PKM2 Mediates Chronic Myeloid Leukemia Imatinib Resistance By Regulating Glycolysis Energy Metabolism
Conclusion: Pyruvate kinase M2 (PKM2) acts as an important rate-limiting enzyme in the aerobic glycolytic pathway, and mediates abnormal metabolic pathways which promote tumor cell proliferation, invasion and drug resistance. Compared to the TKI-sensitive primary cell and cell line, PKM2 was increased in the TKI-resistant primary cell and cell line and related to glycolytic level. PKM2 inhibitor can inhibit CML cells growth, induce cell apoptosis, and combined with IM at a low dose can exhibited a synergistic anti-leukemia effect on TKI-resistant cells. Low dose PKM2 inhibitor combined with IM can enhance targeted killing ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Tong, L., Xu, N., Zhou, X., Huang, J., wan-Er, W., Chen, C., Liang, L., Liu, Q., Xiaoli, L. Tags: 631. Chronic Myeloid Leukemia: Biology and Pathophysiology, excluding Therapy: Poster I Source Type: research

Targeting XIAP Via Degradation of MDM-2 By MX69 in Aggressive Lymphomas
Conclusion: Our data suggests that in vitro exposure of a wide variety of B-cell lymphoma cell lines (including BL, DLBCL, MCL or RRCL) to MX69 resulted in anti-tumor activity. Perhaps related to its anti-tumor effects, MX69 inhibited XIAP levels. These findings are similar to prior SiRNA XIAP knockdown experiments. Strong synergistic activity was observed when XIAP was combined with various chemotherapy agents and small molecules inhibitors (such as Venetoclax, ixazomib or ibrutinib). Ex vivo experiments using primary tumor cells isolated from lymphoma patients and lymphoma mouse models are been planned. Targeting Mdm2 an...
Source: Blood - November 21, 2018 Category: Hematology Authors: Khan, S., Runckel, K., Mavis, C., Barth, M. J., Hernandez-Ilizaliturri, F. J. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents Source Type: research

Targeting Oncoprotein Translation with Rocaglates in MYC-Driven Lymphoma
Background: c-MYC (MYC) is commonly dysregulated in aggressive B cell lymphomas. MYC associated lymphoma, especially Double Hit lymphoma (DHL) and Double-Expression Lymphoma (DEL) which are characterized by MYC and BCL2 dual overexpression usually present with the inferior outcome as rapid disease progression and poor response to standard chemotherapy regimen. Nevertheless, MYC is considered as an "undruggable" target and targeting strategies such as suppressing MYC transcription by bromodomain (BRD)-4 inhibitors have been widely investigated in both preclinical models and clinical trials. However, increasing evidence has ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, X., Bi, C., Lu, T., Yue, T., Zhang, W., Zhang, X., Cheng, W., Tian, T., Lunning, M. A., Vose, J. M., Pelletier, J., Porco, J. A., Tao, J., Fu, K. Tags: 625. Lymphoma: Pre-Clinical-Chemotherapy and Biologic Agents: Specific Pathway Inhibitors 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

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