• Filter By:
• Specialty
• Source
• Condition
• Cancer
• Infectious Disease
• Drug
• Training
• Management
• Procedure
• Therapy
• Vaccine
• Nutrition
• Country

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

PDZ Binding Kinase (PBK) - a Novel Gene Driving Genomic Evolution in Multiple Myeloma
As in all cancers, genomic instability leads to ongoing acquisition of new genetic changes in multiple myeloma (MM). This adaptability underlies the development of drug resistance and progression in MM. This genomic instability is driven by cellular processes, mainly related with DNA repair and perturbed by functional changes in limited number of genes. Since kinases play a critical role in the regulation of biological processes, including DNA damage/repair signaling and are relatively easy to screen for inhibitors, we investigated for novel genes involved in the acquisition of new genomic changes in MM. Using a large geno...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kumar, S., Buon, L., Talluri, S., Shi, J., Avet-Loiseau, H., Samur, M. K., Shammas, M. A., Munshi, N. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

Aurora Kinase a/MDM2-Mediated SETD2 Loss of Function in Chronic Myeloid Leukemia Patients in Blast Crisis Induces Genetic Instability and Can be Therapeutically Targeted
In conclusion, phosphorylation by Aurora Kinase A and ubiquitination by MDM2 contribute to SETD2 non-genomic loss of function in advanced-phase CML. Loss of SETD2/H3K36me3 is associated with increased DNA damage and impaired HR repair. Restoring physiological H3K36me3 levels may help improve the outcome of this critical subset of pts.Acknowledgments: study supported by AIRC (project code 16996) and AIL (Associazione Italiana contro le Leucemia, Linfomi e Mieloma).Figure 1.DisclosuresCastagnetti: Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria; Novartis: Consulta...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mancini, M., De Santis, S., Monaldi, C., Bavaro, L., Martelli, M., Castagnetti, F., Gugliotta, G., Rosti, G., Fontana, M. C., Dan, E., Sinigaglia, B., Iurlo, A., Orofino, N., Abruzzese, E., Salvucci, M., Pregno, P., Gozzini, A., Crugnola, M., Albano, F., Tags: 631. Chronic Myeloid Leukemia: Biology and Pathophysiology, excluding Therapy: Poster I Source Type: research

MDM2 and Aurora Kinase a Contribute to SETD2 Loss of Function in Advanced Systemic Mastocytosis: Implications for Pathogenesis and Treatment
The SETD2 gene encodes the only methyltransferase responsible for histone H3 lysine 36 trimethylation (H3K36Me3) in humans. H3K36me3 play a key role in preserving the fidelity of transcription elongation and splicing. In addition, SETD2/H3K36me3 have more recently been implicated in the maintenance of genomic integrity by regulating homologous recombination (HR) repair, Mismatch Repair (MMR) mitotic spindle assembly and chromosome segregation. SETD2 deletions and/or inactivating mutations occur in many solid tumors and have recently been found also in acute leukemias. We have reported that the HMC-1.1 and -1.2 mast cell le...
Source: Blood - November 21, 2018 Category: Hematology Authors: Mancini, M., Monaldi, C., De Santis, S., Papayannidis, C., Rondoni, M., Bavaro, L., Martelli, M., Maria Chiara, A., Curti, A., Ficarra, E., Paciello, G., Fontana, M. C., Zanotti, R., Bonifacio, M., Scaffidi, L., Pagano, L., Criscuolo, M., Albano, F., Cice Tags: 635. Myeloproliferative Syndromes: Basic Science: Poster I Source Type: research

hnRNP U and DDX47 Are Novel FANCD2 Interactors That May Help to Resolve R-Loops during Mild Replication Stress
Conclusion: We suggest that FANCD2 protects genome stability by recruiting RNA processing enzymes, including hnRNP U or DDX47, to resolve or prevent accumulation of R-loops induced by transcription-replication collisions during mild replication stress. Thus, our study may provide a novel insight to understand the mechanism of bone marrow failure and leukemogenesis in Fanconi anemia patients.DisclosuresTakaori-Kondo: Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria; Janssen Pharmaceuticals: Honoraria.
Source: Blood - November 21, 2018 Category: Hematology Authors: Okamoto, Y., Abe, M., Itaya, A., Tomida, J., Takaori-Kondo, A., Taoka, M., Isobe, T., Takata, M. Tags: 508. Bone Marrow Failure: Poster I 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

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

Prolylcarboxypeptidase promotes angiogenesis and vascular repair
Prolylcarboxypeptidase (PRCP) is associated with leanness, hypertension, and thrombosis. PRCP-depleted mice have injured vessels with reduced Kruppel-like factor (KLF)2, KLF4, endothelial nitric oxide synthase (eNOS), and thrombomodulin. Does PRCP influence vessel growth, angiogenesis, and injury repair? PRCP depletion reduced endothelial cell growth, whereas transfection of hPRCP cDNA enhanced cell proliferation. Transfection of hPRCP cDNA, or an active site mutant (hPRCPmut) rescued reduced cell growth after PRCP siRNA knockdown. PRCP-depleted cells migrated less on scratch assay and murine PRCPgt/gt aortic segments had ...
Source: Blood - August 22, 2013 Category: Hematology Authors: Adams, G. N., Stavrou, E. X., Fang, C., Merkulova, A., Alaiti, M. A., Nakajima, K., Morooka, T., Merkulov, S., LaRusch, G. A., Simon, D. I., Jain, M. K., Schmaier, A. H. Tags: Vascular Biology Source Type: research