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Total 71 results found since Jan 2013.
Matrix Metalloproteinase and Tissue Inhibitor of Metalloproteinases Is Associated with Multiple Myeloma Progression, Prognosis and Extramedullary Plasmacytoma
Conclusions: Our results suggest that TIMP1, 2 and MMP14, 24 were associated with EMP formation. Among those factors, TIMP1 is the one which may play a key role for MM progression and chemo-resistance based on the results revealing its upregulation by antineoplastic agents and association with poor prognosis of MM patients. Our results is consistent with a previous report describing that high serum TIMP1 concentration was associated with poor prognosis of MM. TIMP is recently shown to play another role besides negative regulator for MMP, so further study to elucidate its specific role for chemo-resistance contributes to de...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ishihara, R., Murakami, Y., Homma, K., Watanabe, S., Oda, T., Sunaga, M., Yamane, E., Kobayashi, N., Osaki, Y., Ishizaki, T., Shimizu, H., Iriuchishima, H., Koiso, H., Tsukamoto, N., Yokohama, A., Nanami, G., Ino, R., Saitoh, T., Murakami, H., Handa, H. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II 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
CLIC1 Cooperates with Integrins to Promote Thrombus Formation and Angiogenesis
Chloride intracellular channel 1 (CLIC1) is a member of a family of six highly homologous membrane proteins (CLIC1-6), which have been shown to be co-regulated with integrins suggesting their involvement in cell adhesion, migration and proliferation. CLIC1 is a metamorphic protein that functions as an oxidoreductase in the cytoplasm as well as an ion channel in the cell membrane. CLIC1 is upregulated in angiogenic endothelial and metastatic tumor cells. In addition, studies in CLIC1 knockout mice have shown that CLIC1 promotes platelet function. Here, we hypothesize that CLIC1 supports cell adhesive functions in platelets ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Knowles, L. M., Ampofo, E., Menger, M. D., Niewald, P., Drawz, A., Eichler, H., Pilch, J. Tags: 301. Vascular Wall Biology, Endothelial Progenitor Cells, and Platelet Adhesion, Activation, and Biochemistry: Poster II 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
Effective Lipidoid Nanoparticle Delivery In Vivo of siRNA Targeting Kappa Light Chain Production in a Murine Xenograft Model
CONCLUSIONS: We have previously shown that siIGKC, a pool of siRNA directed at consensus sequences in the LC constant region gene, can significantly reduce LC production in clonal plasma cells from patients, in human myeloma cell lines, and in vivo in a flank plasmacytoma xenograft model. In this work, we show that 8B-3 is a promising LPN for delivery of siRNA to human plasma cells and, when loaded with siIGKC, can with relative safety significantly reduce circulating LC in the NSG JJN3 IP model after 3 daily IP injections despite rapid tumor growth. We also show the utility of the NSG JJN3 IP model for the study of LC dir...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ma, X., Zhou, P., Kugelmass, A., Toskic, D., Warner, M., Lee, L. X., Fogaren, T., Wang, M., Li, Y., Yang, L., Xu, Q., Comenzo, R. Tags: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: 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
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
SLN124, a Galnac-siRNA Conjugate Targeting TMPRSS6, for the Treatment of Iron Overload and Ineffective Erythropoiesis Such As in Beta-Thalassemia
Accumulation of excess iron in tissues causes organ damage and dysfunction and may lead to serious clinical consequences including liver cirrhosis, diabetes, growth retardation and heart failure. Iron overload is a major health threat in iron loading anemias, like beta-thalassemia, myelodysplastic syndrome and in hereditary hemochromatosis. In patients with beta-thalassemia major, iron overload develops due to frequent blood transfusions to control the severe anemia. In addition, iron overload also occurs in patients with beta thalassemia intermedia (non-transfusion dependent beta-thalassemia). In the later cases, iron ove...
Source: Blood - November 21, 2018 Category: Hematology Authors: Altamura, S., Altamura, S., Muckenthaler, M. U., Dames, S., Frauendorf, C., Schubert, S., Aleku, M., Vadolas, J., Grigoriadis, G., Zugel, U. Tags: 102. Regulation of Iron Metabolism: Poster II Source Type: research
HMGB1 Interacts with the MLL-AF4 Fusion Complex to Regulate Pro-Leukemic Gene Transcription in Infant Acute Lymphoblastic Leukemia
In this study, we generated an HMGB1 siRNA knockdown in primary MLL-ALL cells from 3 infants to test our hypothesis that HMGB1-MLL interactions regulate pro-leukemic gene expression and represent a rational therapeutic target.CD19-selected leukemic blasts were isolated from the cryopreserved bone marrow or peripheral blood specimens of 3 infants with cytogenetically confirmed MLL-AF4 rearrangements. HMGB1 knockdown was confirmed by comparing HMGB1 mRNA and protein expression, by qPCR and Western Blot, in cells transfected with HMGB1 vs. control sequence siRNA. First, determined whether HMGB1 knockdown affected expression o...
Source: Blood - November 21, 2018 Category: Hematology Authors: Toia, L. M., Braverman, E. L., Magno, J. A., Shand, J. C. Tags: 602. Disordered Gene Expression in Hematologic Malignancy, including Disordered Epigenetic Regulation: Poster II Source Type: research
Overexpressed Melk Promotes the Stability of EZH2 through Phosphorylation in Natural Killer/T Cell Lymphoma (NKTL)
In this study, we examined EZH2 protein turnover mechanisms in the NKTL context.The serine/threonine kinase Melk is one of the overexpressed genes in NKTL patient samples and cell lines, and the interaction between Melk and EZH2 was established by co-immunoprecipitation. Inhibition of Melk using inhibitor or siRNA both resulted in a decrease of EZH2 protein levels in NKTL cells, whereas there was no change in the mRNA level of EZH2, suggesting that Melk regulated EZH2 at the protein level. Next, we observed a change of EZH2 ubiquitination upon manipulation of Melk expression.Next, in order to confirm that Melk truly affect...
Source: Blood - November 21, 2018 Category: Hematology Authors: Li, B., Kappei, D., Yan, J., Eichhorn, P., Ng, S. B., Chng, W. J. Tags: 622. Lymphoma Biology-Non-Genetic Studies: Poster II Source Type: research
SHP1 Deficiency Is Responsible for the Constitutive Activation of the BCR Pathway in GCB DLBCL
In this study, we investigated whether activation of the BCR pathway in GCB DLBCL is potentially caused by deficiency of the phosphatase SHP1, which is an important negative regulator of the BCR pathway and has been reported to be downregulated in approximately 40% of primary DLBCL tumors. For this purpose, we first correlated SHP1 expression with the presence of phosphorylated SYK and BLNK in the GCB DLBCL cell lines OCI-Ly1, OCI-Ly7, OCI-Ly18, SU-DHL-4, SU-DHL-6, WSU-NHL, SU-DHL-8, Toledo, BJAB, OCI-Ly19, OCI-Ly4, and Farage. Immunoblotting analysis revealed that SHP1 is expressed in SU-DHL-8, Toledo, BJAB, OCI-Ly19, OCI...
Source: Blood - November 21, 2018 Category: Hematology Authors: Sasi, B. K., Turkalj, S., Kalkan, H., Porro, F., Bojnik, E., Pyrzynska, B., Zerrouqi, A., Bobrowicz, M., Winiarska, M., Priebe, V., Bertoni, F., Mansouri, L., Rosenquist, R., Efremov, D. G. Tags: 622. Lymphoma Biology-Non-Genetic Studies: Poster II Source Type: research
Wnt5a Induces Association of ROR1 with Ca2+/Calmodulin-Dependent Protein Kinase II and ROR1-Dependent Calcium Influx in Chronic Lymphocytic Leukemia
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncoembryonic antigen that is expressed on CLL cells, but not on normal postpartum tissues. We found that ROR1 was a receptor for Wnt5a, which could enhance CLL-cell proliferation (Yu J, et al, JCI 126:585, 2016; Yu J, et al, Leukemia 31:2608, 2017; Hasan MK, et al, Blood 132:170, 2018). We performed mass spectrometry-based proteomics to interrogate immune-precipitates of Wnt5a-activated ROR1 and identified Ca2+/calmodulin-dependent protein kinase II (CaMKII), a serine/threonine-specific protein kinase. Recent studies demonstrated that high levels of different is...
Source: Blood - November 21, 2018 Category: Hematology Authors: Chen, L., Chen, Y., Yu, J., Zhang, L., Rassenti, L. Z., Kipps, T. J. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster I Source Type: research
Concomitant Targeting of FLT3 and BTK with CG'806 Overcomes FLT3-Inhibitor Resistance through Inhibition of Autophagy
Fms-like tyrosine kinase 3 (FLT3)-targeted therapy represents an important paradigm in the management of patients with highly aggressive FLT3 mutated acute myeloid leukemia (AML). However, clinical efficacy is usually transient and followed by emergence of resistance to FLT3-inhibitors (Borthakur et al., 2011; Cortes et al., 2013; Zhang et al., 2008). Such resistance often results from acquired mutations of TKD, which are frequently identified in D835, Y842 and F691 residues (Smith et al., 2015; Smith et al., 2012; Zhang et al., 2014). It was reported that the FLT3-ITD-targeting drug sorafenib can induce autophagy in human...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, W., Yu, G., Zhang, H., Ly, C., Yuan, B., Ruvolo, V., Piya, S., Bhattacharya, S., Zhang, Q., Borthakur, G., Battula, V. L., Konopleva, M. Y., Rice, W. G., Andreeff, M. Tags: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster II Source Type: research
Cirmtuzumab Inhibits Non-Canonical Wnt Signaling without Enhancing Canonical Wnt/{beta}-Catenin Signaling in Chronic Lymphocytic Leukemia
In this study, we examined whether genetic silencing of ROR1 or inhibition of ROR1-signaling also could influence canonical Wnt signaling. To inhibit ROR1 signaling we used the humanized anti-ROR1 mAb cirmtuzumab, which is being evaluated in patients with CLL (Choi MY, et al, Cell Stem Cell, 22:951, 2018). Surprisingly, we found that CRISPR/Cas9 deletion of ROR1 in 293T cells also could enhance the capacity of Wnt3a to activate canonical Wnt-signaling, albeit to a lesser extent than CRISPR/Cas9 deletion of ROR2; conversely, re-introduction of ROR1 into ROR1-deleted 293T cells suppressed Wnt3a-induced activation of canonica...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, H., Zhang, S., Ghia, E. M., Choi, M. Y., Zhang, J., Chen, L., Widhopf II, G. F., Rassenti, L. Z., Kipps, T. J. Tags: 605. Molecular Pharmacology, Drug Resistance-Lymphoid and Other Diseases: Poster II Source Type: research
