Hematology
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SGO: Drug Combination Slows Recurrent Ovarian Cancer (CME/CE)
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SAN FRANCISCO (MedPage Today) -- Combination chemotherapy resulted in a longer, progression-free survival (PFS) than did sequential therapy in a randomized clinical trial of patients with recurrent, platinum-sensitive ovarian cancer. (Source: MedPage Today Hematology/Oncology)
Source: MedPage Today Hematology/Oncology - March 15, 2010 Category: Hematology Source Type: news
Risk Stratification Imperative To Treatment Selection In Patients With AML
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Using risk stratification to assist in treatment selection was just one of the focal points at a recent presentation of the NCCN Clinical Practice Guidelines for Oncology (NCCN Guidelines™) for Acute Myeloid Leukemia (AML) at the NCCN 15th Annual Conference. B... (Source: Lymphoma / Leukemia News From Medical News Today)
Source: Lymphoma / Leukemia News From Medical News Today - March 15, 2010 Category: Hematology Tags: Lymphoma / Leukemia / Myeloma Source Type: news
Anemia management in chronic kidney disease: Intravenous iron steps forward
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No abstract. (Source: American Journal of Hematology)
Source: American Journal of Hematology - March 15, 2010 Category: Hematology Authors: Daniel W. Coyne, Michael Auerbach Source Type: journals
Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease
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& J C Voltarelli (Source: Bone Marrow Transplantation)
Source: Bone Marrow Transplantation - March 15, 2010 Category: Hematology Authors: D F GodoiC R CardosoD B FerrazP R ProvinciattoF Q CunhaJ S SilvaJ C Voltarelli Tags: high-dose chemotherapy hematopoietic SCT inflammatory bowel disease immune response Source Type: journals
Delayed neutrophil engraftment in cord blood transplantation with intensive administration of mycophenolate mofetil for GVHD prophylaxis
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Katayama
& T Matsui (Source: Bone Marrow Transplantation)
Source: Bone Marrow Transplantation - March 15, 2010 Category: Hematology Authors: A OkamuraM ShimoyamaS IshiiK WakahashiN AsadaH KawanoY KawamoriS NishikawaK MinagawaY KatayamaT Matsui Source Type: journals
The impact of novel influenza A (H1N1) after hematopoietic SCT
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& D Rondelli (Source: Bone Marrow Transplantation)
Source: Bone Marrow Transplantation - March 15, 2010 Category: Hematology Authors: P PatelK SweissS ShataviD PeaceN ClarkD Rondelli Source Type: journals
Observational prospective study of viral infections in children undergoing allogeneic hematopoietic cell transplantation: a 3-year GETMON experience
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mez, M E González, A Muñoz
& M A Díaz (Source: Bone Marrow Transplantation)
Source: Bone Marrow Transplantation - March 15, 2010 Category: Hematology Authors: A VerdeguerC D de HerediaM GonzálezA M MartínezJ M Fernández-NavarroJ M Pérez-HurtadoI BadellP GómezM E GonzálezA MuñozM A Díaz Tags: viral infection hematopoietic cell transplantation children Source Type: journals
Bevacizumab in combination with sequential high-dose chemotherapy in solid cancer, a feasibility study
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ld
& H J Schmoll (Source: Bone Marrow Transplantation)
Source: Bone Marrow Transplantation - March 15, 2010 Category: Hematology Authors: K JordanH H WolfW VoigtT KegelL P MuellerT BehlendorfC SippelD ArnoldH J Schmoll Tags: high-dose chemotherapy bevacizumab sarcoma germ cell cancer Source Type: journals
Impact of GvHD on quality of life in long-term survivors of haematopoietic transplantation
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eger
& B Holzner (Source: Bone Marrow Transplantation)
Source: Bone Marrow Transplantation - March 15, 2010 Category: Hematology Authors: S PalluaJ GiesingerA OberguggenbergerG KemmlerD NachbaurJ ClausenM KoppB Sperner-UnterwegerB Holzner Tags: GvHD quality of life PBSC transplantation survivor Source Type: journals
Identification of molecular markers for pre-engraftment immune reactions after cord blood transplantation by SELDI-TOF MS
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, Y Takaue
& Y Heike (Source: Bone Marrow Transplantation)
Source: Bone Marrow Transplantation - March 15, 2010 Category: Hematology Authors: Y Morita-HoshiS-I MoriA SoedaT WakedaY OhsakiM ShiwaK MasuokaA WakeS TaniguchiY TakaueY Heike Tags: serum amyloid A pre-engraftment immune reactions cord blood transplantation SELDI-TOF MS Source Type: journals
Top-up transfusions in neonates with Rh hemolytic disease in relation to exchange transfusions
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Conclusion In this study, restrictive ET criteria in neonates with Rh hemolytic disease lead to a reduction of the rate of ET but an increase in the number of top-up transfusions for neonatal anemia. (Source: Vox Sanguinis)
Source: Vox Sanguinis - March 15, 2010 Category: Hematology Authors: M. E. A. Rath, V. E. H. J. Smits-Wintjens, I. Lindenburg, A. Brand, D. Oepkes, F. J. Walther, E. Lopriore Source Type: journals
MiRNA profiling in B non-Hodgkin lymphoma: a MYC-related miRNA profile characterizes Burkitt lymphoma
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - March 15, 2010 Category: Hematology Authors: Jan-Lukas Robertus, Joost Kluiver, Callista Weggemans, Geert Harms, Rogier M. Reijmers, Yolanthe Swart, Klaas Kok, Stefano Rosati, Ed Schuuring, Gustaaf van Imhoff, Steven T. Pals, Philip Kluin, Anke van den Berg Source Type: journals
Guideline for investigation and management of adults and children presenting with a thrombocytosis
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - March 15, 2010 Category: Hematology Authors: Claire N. Harrison, David Bareford, Nauman Butt, Peter Campbell, Eibhlean Conneally, Mark Drummond, Wendy Erber, Tamara Everington, Anthony R. Green, Georgina W. Hall, Beverley J. Hunt, Christopher A. Ludlam, Richard Murrin, Catherine Nelson-Piercy, Deept Source Type: journals
Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585
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This study preclinically evaluated the effects of the 'second generation' pan-HDAC inhibitor JNJ-26481585 on human multiple myeloma (MM) cells from established cell lines and primary MM samples (n = 42). Molecular responses in both groups of MM cells included histone acetylation, a shift in Bcl2-family members towards proapoptotic bias, attenuation of growth and survival pathway activity and Hsp72 induction. Mcl-1 depletion and Hsp72 induction were the most reliable features observed in JNJ-26481585-treated primary MM samples. The drug alone effectively induced myeloma cell death at low nanomolar concentrations. In vitro c...
Source: British Journal of Haematology - March 15, 2010 Category: Hematology Authors: Thorsten Stühmer, Janine Arts, Manik Chatterjee, Johanna Borawski, André Wolff, Peter King, Hermann Einsele, Eugen Leo, Ralf C. Bargou Source Type: journals
Comparison of intradialytic blood pressure variability between conventional thrice-weekly hemodialysis and short daily hemodialysis
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We examined the effect of short daily hemodialysis (SDHD) on intradialytic BP variability relative to conventional thrice-weekly HD (CHD). This is a retrospective cohort study. Subjects were those converted from CHD to SDHD (n=12). All intradialytic BPs were collected on the last month of CHD, and on month 6 of SDHD. Absolute predialysis BP level and intradialytic BP variability were defined as the intercept and average residual terms, respectively, from a mixed-effects linear regression model of time on BP. Dialysis modality was a predictor variable (CHD vs. SDHD). Outcome variables were intradialytic BP variability and h...
Source: Hemodialysis International - March 15, 2010 Category: Hematology Authors: Miho MURASHIMA, Dinesh KUMAR, Alden M. DOYLE, Joel D. GLICKMAN Source Type: journals
Pfizer Halts Trial, Two Others Miss Primary Endpoint
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Pfizer has halted another phase-III trial of figitumumab and two trials of sunitinib in breast cancer failed to show significant improvement in survival. (Source: MedPage Today Hematology/Oncology)
Source: MedPage Today Hematology/Oncology - March 14, 2010 Category: Hematology Source Type: news
Development and utility of a multi-dimensional grid to assess individual mineral metabolism control in hemodialysis patients: A potential aid for therapeutic decision making?
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A grid was developed to evaluate control of serum calcium, phosphate, and parathyroid hormone levels in hemodialysis patients, based on guideline recommendations (National Kidney Foundation Kidney Disease Outcomes Quality Initiative and Canadian Society of Nephrology), and its face validity was examined in a representative sample of Canadian patients. A retrospective chart review was undertaken in hemodialysis patients from 7 Canadian units. Patients >18 years, on hemodialysis for [ge]12 months, and [ge]3 parathyroid hormone levels measured [ge]1 month apart were included. The grid classified mineral metabolism control as ...
Source: Hemodialysis International - March 14, 2010 Category: Hematology Authors: A. Ross MORTON, Sean MURPHY, David HIRSCH, Martine LEBLANC, Paul BARRÉ, Charmaine LOK, Gavril HERCZ, Anthony HODSMAN, Martina RESLEROVA, Adeera LEVIN Source Type: journals
FDA Approves Five-Day Dosing Regimen For Dacogen(R) (decitabine) For Injection, Offering A New Outpatient Dosing Option For Myelodysplastic Syndromes
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Eisai Inc announced that the U.S. Food and Drug Administration (FDA) has approved a five-day dosing regimen for Dacogen® (decitabine) for Injection to treat patients with myelodysplastic syndromes (MDS), a group of bone marrow diseases that alter the production of functional blood cells... (Source: Lymphoma / Leukemia News From Medical News Today)
Source: Lymphoma / Leukemia News From Medical News Today - March 13, 2010 Category: Hematology Tags: Lymphoma / Leukemia / Myeloma Source Type: news
RRM1 single nucleotide polymorphism -37C->A correlates with progression-free survival in NSCLC patients after gemcitabine-based chemotherapy
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Conclusions:
The RRM1 polymorphism 37C->A correlated with PFS in NSCLC patients treated with gemcitabine-based chemotherapy. No significant correlation was found between PBMC RRM1 mRNA expression and the efficacy of gemcitabine. (Source: Journal of Hematology and Oncology)
Source: Journal of Hematology and Oncology - March 13, 2010 Category: Hematology Authors: Song DongAi-Lin GuoZhi-Hong ChenZhen WangXu-Chao ZhangYing HangZhi XieHong-Hong YanHua ChengYi-Long Wu Source Type: journals
Whole-body MRI for staging Hodgkin lymphoma in a pregnant patient
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No abstract. (Source: American Journal of Hematology)
Source: American Journal of Hematology - March 13, 2010 Category: Hematology Authors: Malou A. Vermoolen, Thomas C. Kwee, Rutger A.J. Nievelstein Source Type: journals
Impaired lymphocyte mitochondrial antioxidant defences in variegate porphyria are accompanied by more inducible reactive oxygen species production and DNA damage
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In conclusion, lymphocytes from VP women showed impaired expression of mitochondrial antioxidant defences but no significant signs of oxidative stress were evidenced in basal, non-stressing conditions; however, lymphocytes of VP women were more susceptible to producing mitochondrial ROS and to suffering oxidative damage when submitted to stressful situations. (Source: British Journal of Haematology)
Source: British Journal of Haematology - March 13, 2010 Category: Hematology Authors: Miguel D. Ferrer, Antoni Sureda, Pedro Tauler, Clara Palacín, Josep A. Tur, Antoni Pons Source Type: journals
Home Specimen Collection Boosts Cervical Cancer Screening (CME/CE)
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Allowing women to collect their own cervicovaginal lavage specimens for human papillomavirus (HPV) testing increased coverage and cervical abnormality detection rates in a community-based cervical cancer screening program, Dutch researchers said. (Source: MedPage Today Hematology/Oncology)
Source: MedPage Today Hematology/Oncology - March 12, 2010 Category: Hematology Source Type: news
Highlights of the fifth annual platelet colloquium
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Content Type Journal ArticleDOI 10.1007/s11239-010-0468-2Authors
Patricia A. French, Left Lane Communications Chapel Hill NC USA
Journal Journal of Thrombosis and ThrombolysisOnline ISSN 1573-742XPrint ISSN 0929-5305 (Source: Journal of Thrombosis and Thrombolysis)
Source: Journal of Thrombosis and Thrombolysis - March 12, 2010 Category: Hematology Tags: Journal of Thrombosis and Thrombolysis Source Type: journals
Heart rate variability during and after peripheral blood stem cell leukapheresis in autologous transplant patients and allogeneic transplant donors.
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Side effects of varying severity are frequent in peripheral blood stem cell harvest (PBSCH). Life-threatening complications associated with PBSCH have also been reported. Heart rate variability (HRV), which reflects sympathovagal balance and autonomic cardiovascular control, has been a subject of intense interest in various diseases precipitating sudden death. Here, we prospectively assessed the impact of leukapheresis on HRV among autologous hematopoietic cell transplant patients and healthy donors. We found that HRV indicators, the standard deviation of normal-to-normal intervals (SDNN) value, the square root of the ...
Source: International Journal of Hematology - March 12, 2010 Category: Hematology Authors: Nakane T, Nakamae H, Koh H, Nakamae M, Aimoto R, Terada Y, Koh KR, Yamane T, Hino M Tags: Int J Hematol Source Type: journals
Successful unrelated donor cord blood transplantation for chronic granulomatous disease.
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This report exemplified a success of unrelated donor cord blood transplantation (CBT) in a 4-month-old boy with chronic granulomatous disease (CGD). Following Bu14/Cy200/ATG conditioning, the patient received an HLA 2-locus-mismatched cord blood unit, and the total number of infused nucleated cells was 11.52 x 10(7)/kg. Neutrophil engraftment was achieved on day +13, and a platelet count greater than 20 x 10(9)/L was achieved on day +50. The neutrophil oxidative burst was 100% normal with full donor lymphocyte reconstitution at 8 months post-transplant. This case highlights that unrelated donor CBT for CGD is potentially s...
Source: International Journal of Hematology - March 12, 2010 Category: Hematology Authors: Jaing TH, Lee WI, Cheng PJ, Chen SH, Huang JL, Soong YK Tags: Int J Hematol Source Type: journals
Differentiation of mesodermal cells from pluripotent stem cells.
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The pluripotency of embryonic stem cells has been well demonstrated by a vast variety of studies showing the induction of differentiation into desired cell types that have the potential to be used not only in basic studies but also in medical applications. The induction of mesodermal cells, especially blood cells, from embryonic stem cells is notable from the point of view of transplantation, and the methods for this induction have improved over the last few years, with more defined culture conditions in place. Concurrently, the generation of induced pluripotent stem cells from somatic cells opens the possibility of au...
Source: International Journal of Hematology - March 12, 2010 Category: Hematology Authors: Kitagawa M, Era T Tags: Int J Hematol Source Type: journals
Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo
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This study investigated the cytotoxicity and mechanism of action of AS703026, a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma (MM). AS703026 inhibited growth and survival of MM cells and cytokine-induced osteoclast differentiation more potently (9- to 10-fold) than AZD6244. Inhibition of proliferation induced by AS703026 was mediated by G0-G1 cell cycle arrest and was accompanied by reduction of MAF oncogene expression. AS703026 further induced apoptosis via caspase 3 and Poly ADP ribose polymerase (PARP) cleavage in MM cells, both in the presence or absence of bone marrow stromal cells ...
Source: British Journal of Haematology - March 12, 2010 Category: Hematology Authors: Kihyun Kim, Sun-Young Kong, Mariateresa Fulciniti, Xianfeng Li, Weihua Song, Sabikun Nahar, Peter Burger, Mathew J. Rumizen, Klaus Podar, Dharminder Chauhan, Teru Hideshima, Nikhil C. Munshi, Paul Richardson, Ann Clark, Janet Ogden, Andreas Goutopoulos, L Source Type: journals
Pharmacodynamic and efficacy studies of the novel proteasome inhibitor NPI-0052 (marizomib) in a human plasmacytoma xenograft murine model
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Our previous study showed that the novel proteasome inhibitor NPI-0052 induces apoptosis in multiple myeloma (MM) cells resistant to conventional and bortezomib (Velcade[trade], Takeda, Boston, MA, USA) therapies. In vivo studies using human MM-xenografts demonstrated that NPI-0052 is well tolerated, prolongs survival, and reduces tumour recurrence. These preclinical studies provided the basis for an ongoing phase-1 clinical trial of NPI-0052 in relapsed/refractory MM patients. Here we performed pharmacodynamic (PD) studies of NPI-0052 using human MM xenograft murine model. Our results showed that NPI-0052: (i) rapidly lef...
Source: British Journal of Haematology - March 12, 2010 Category: Hematology Authors: Ajita V. Singh, Michael A. Palladino, George Kenneth Lloyd, Barbara C. Potts, Dharminder Chauhan, Kenneth C. Anderson Source Type: journals
Chromosome 9p24 abnormalities: prevalence, description of novel JAK2 translocations, JAK2V617F mutation analysis and clinicopathologic correlates
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Conclusions: Chromosome 9p24 abnormalities are rare and do not always involve JAK2. The subset with JAK2 translocations are usually associated with MPN and harbor JAK2V617F, suggesting a cause-effect relationship. The current study also describes five novel translocations involving JAK2. (Source: European Journal of Haematology)
Source: European Journal of Haematology - March 12, 2010 Category: Hematology Authors: Mrinal M. Patnaik, Ryan A. Knudson, Naseema Gangat, Curtis A. Hanson, Animesh Pardanani, Ayalew Tefferi, Rhett P. Ketterling Source Type: journals
The prevalence of factor VIII inhibitors and genetic aspects of inhibitor development in Chinese patients with haemophilia A
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In conclusion, the prevalence of inhibitors in Chinese HA patients is much lower than that reported for other ethnic groups and the large deletion and nonsense mutations are high risk factors for high titre inhibitor development. (Source: Haemophilia)
Source: Haemophilia - March 12, 2010 Category: Hematology Authors: X. F. WANG, Y. Q. ZHAO, R. C. YANG, J. S. WU, J. SUN, X. S. ZHANG, Q. L. DING, H. L. GE, H. L. WANG Source Type: journals
Hairy cell leukaemia-variant and splenic red pulp lymphoma: a single entity?
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(Source: British Journal of Haematology)
Source: British Journal of Haematology - March 12, 2010 Category: Hematology Authors: Alexandra Traverse-Glehen, Lucile Baseggio, Evelyne Callet-Bauchu, Martine Ffrench, Bertrand Coiffier, Gilles Salles, Pascale Felman, Francoise Berger Source Type: journals
Response: Estimating frequency of cancer stem cells in a mouse model of adult T-cell leukemia/lymphoma
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(Source: Blood)
Source: Blood - March 11, 2010 Category: Hematology Authors: Yamazaki, J., Mizukami, T., Hall, W. W., Hamaguchi, I. Tags: CORRESPONDENCE Source Type: journals
Challenging the adult T-cell leukemia/lymphoma (ATL) stem cell concept based on limiting dilution transplantation assay
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(Source: Blood)
Source: Blood - March 11, 2010 Category: Hematology Authors: Bonnefoix, T., Callanan, M. Tags: CORRESPONDENCE Source Type: journals
15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Src-mediated Egr-1-dependent rapid induction of FGF-2 expression
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To understand the mechanisms underlying 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE]–induced angiogenesis, we studied the role of Egr-1. 15(S)-HETE induced Egr-1 expression in a time-dependent manner in human dermal microvascular endothelial cells (HDMVECs). Blockade of Egr-1 via forced expression of its dominant-negative mutant attenuated 15(S)-HETE–induced HDMVEC migration and tube formation as well as Matrigel plug angiogenesis. 15(S)-HETE–induced Egr-1 expression requires Src activation. In addition, adenovirus-mediated expression of dominant-negative mutant of Src blocked 15(S)-HETE's effects on m...
Source: Blood - March 11, 2010 Category: Hematology Authors: Kundumani-Sridharan, V., Niu, J., Wang, D., Van Quyen, D., Zhang, Q., Singh, N. K., Subramani, J., Karri, S., Rao, G. N. Tags: Vascular Biology Source Type: journals
Induction of tolerance to bone marrow allografts by donor-derived host nonreactive ex vivo-induced central memory CD8 T cells
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In conclusion, anti–third-party Tcms, which home to recipient LNs and effectively delete antidonor T cells, could provide an effective and novel tool for overcoming rejection of BM allografts. (Source: Blood)
Source: Blood - March 11, 2010 Category: Hematology Authors: Ophir, E., Eidelstein, Y., Afik, R., Bachar-Lustig, E., Reisner, Y. Tags: Transplantation Source Type: journals
Human rhinovirus and coronavirus detection among allogeneic hematopoietic stem cell transplantation recipients
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Little is known about clinical and virologic manifestations of rhinovirus (HRV) and coronavirus (HCoV) infections after hematopoietic cell transplantation (HCT). We performed surveillance for 1 year and describe the natural history of these infections during the first 100 days after allogeneic HCT, when symptom surveys and upper respiratory samples were collected weekly. Samples were tested using RT-PCR for HRVs and HCoVs (OC43, 229E, HKU1, and NL63). Among 215 patients, 64 (30%) patients had 67 infections. Day 100 cumulative incidence estimate was 22.3% for HRV and 11.1% for HCoV. Median duration of viral shedding was 3 w...
Source: Blood - March 11, 2010 Category: Hematology Authors: Milano, F., Campbell, A. P., Guthrie, K. A., Kuypers, J., Englund, J. A., Corey, L., Boeckh, M. Tags: Transplantation, Free Research Articles, Clinical Trials and Observations Source Type: journals
Antibodies specifically target AML antigen NuSAP1 after allogeneic bone marrow transplantation
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Identifying the targets of immune response after allogeneic hematopoietic cell transplantation (HCT) promises to provide relevant immune therapy candidate proteins. We used protein microarrays to serologically identify nucleolar and spindle-associated protein 1 (NuSAP1) and chromatin assembly factor 1, subunit B (p60; CHAF1b) as targets of new antibody responses that developed after allogeneic HCT. Western blots and enzyme-linked immunosorbent assays (ELISA) validated their post-HCT recognition and enabled ELISA testing of 120 other patients with various malignancies who underwent allo-HCT. CHAF1b-specific antibodies were ...
Source: Blood - March 11, 2010 Category: Hematology Authors: Wadia, P. P., Coram, M., Armstrong, R. J., Mindrinos, M., Butte, A. J., Miklos, D. B. Tags: Immunobiology, Transplantation, Myeloid Neoplasia Source Type: journals
The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution
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The molecular basis of the HNA-3a/b (5b/a) leukocyte antigen system has not yet been defined despite evidence that HNA-3a–specific antibodies are particularly prone to cause severe, often fatal, transfusion-related lung injury. We used genome-wide single nucleotide polymorphism scanning and sequencing of DNA from persons of different HNA-3a/b phenotypes to identify a single single nucleotide polymorphism in exon 7 of the CLT2 gene (SLC44A2) that predicts an amino acid substitution in the first extracellular loop of choline transporter-like protein 2, a member of the choline transporter-like protein family of membrane...
Source: Blood - March 11, 2010 Category: Hematology Authors: Curtis, B. R., Cox, N. J., Sullivan, M. J., Konkashbaev, A., Bowens, K., Hansen, K., Aster, R. H. Tags: Transfusion Medicine, Brief Reports Source Type: journals
Molecular characterization of in-frame and out-of-frame alternative splicings in coagulation factor XI pre-mRNA
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Alternative splicing of pre-mRNAs is a central process to the generation of proteome complexity. However, many alternative mRNA isoforms carry premature termination codons (PTCs) rendering them possible targets for the nonsense-mediated mRNA decay (NMD) pathway. The F11 gene consists of 15 exons spanning approximately 23 kb on chromosome 4q35 and codes for coagulation factor XI (FXI), a 160-kDa dimeric zymogen composed of 4 apple domains and a serine protease domain. Here, we characterized the F11 splicing pattern in human liver and platelets identifying multiple in-frame and out-of-frame splicing events. Inhibition of NMD...
Source: Blood - March 11, 2010 Category: Hematology Authors: Asselta, R., Rimoldi, V., Guella, I., Solda, G., De Cristofaro, R., Peyvandi, F., Duga, S. Tags: Thrombosis and Hemostasis Source Type: journals
Prolonged activity of factor IX as a monomeric Fc fusion protein
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Treatment of hemophilia B requires frequent infusions of factor IX (FIX) to prophylax against bleeding episodes. Hemophilia B management would benefit from a FIX protein with an extended half-life. A recombinant fusion protein (rFIXFc) containing a single FIX molecule attached to the Fc region of immunoglobulin G was administered intravenously and found to have an extended half-life, compared with recombinant FIX (rFIX) in normal mice, rats, monkeys, and FIX-deficient mice and dogs. Recombinant FIXFc protein concentration was determined in all species, and rFIXFc activity was measured in FIX-deficient animals. The half-lif...
Source: Blood - March 11, 2010 Category: Hematology Authors: Peters, R. T., Low, S. C., Kamphaus, G. D., Dumont, J. A., Amari, J. V., Lu, Q., Zarbis-Papastoitsis, G., Reidy, T. J., Merricks, E. P., Nichols, T. C., Bitonti, A. J. Tags: Thrombosis and Hemostasis Source Type: journals
Fibrinolytic cross-talk: a new mechanism for plasmin formation
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We report here the existence of a fibrinolytic cross-talk mechanism bypassing the requirement for their molecular coassembly on the same surface. First, we demonstrate that, despite impaired binding of Glu-plasminogen to the cell membrane by -aminocaproic acid (-ACA) or by a lysine-binding site–specific mAb, plasmin is unexpectedly formed by cell-associated urokinase (uPA). Second, we show that Glu-plasminogen bound to carboxy-terminal lysine residues in platelets, fibrin, or extracellular matrix components (fibronectin, laminin) is transformed into plasmin by uPA expressed on monocytes or endothelial cell–deri...
Source: Blood - March 11, 2010 Category: Hematology Authors: Dejouvencel, T., Doeuvre, L., Lacroix, R., Plawinski, L., Dignat-George, F., Lijnen, H. R., Angles-Cano, E. Tags: Thrombosis and Hemostasis Source Type: journals
Plasminogen activator inhibitor-1 (PAI-1) is cardioprotective in mice by maintaining microvascular integrity and cardiac architecture
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Although the involvement of plasminogen activator inhibitor-1 (PAI-1) in fibrotic diseases is well documented, its role in cardiac fibrosis remains controversial. The goal of this study was to determine the effect of a PAI-1 deficiency (PAI-1–/–) on the spontaneous development of cardiac fibrosis. PAI-1–/– mice developed pervasive cardiac fibrosis spontaneously with aging, and these mice displayed progressively distorted cardiac architecture and markedly reduced cardiac function. To mechanistically elucidate the role of PAI-1 in cardiac fibrosis, 12-week-old mice were chosen to study the biologic ev...
Source: Blood - March 11, 2010 Category: Hematology Authors: Xu, Z., Castellino, F. J., Ploplis, V. A. Tags: Thrombosis and Hemostasis Source Type: journals
H4R3 methylation facilitates {beta}-globin transcription by regulating histone acetyltransferase binding and H3 acetylation
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We report here that the targeted recruitment of asymmetric dimethyl H4R3 catalyzed by PRMT1 (protein arginine methyltransferase 1) facilitates histone H3 acetylation on Lys9/Lys14. Dimethyl H4R3 provides a binding surface for P300/CBP-associated factor (PCAF) and directly enhances histone H3 acetylation in vitro. We show that these active modifications are essential for efficient interactions between the LCR and the βmaj-promoter as well as transcription of the β-globin gene. Furthermore, knockdown (KD) of PRMT1 by RNA interference in erythroid progenitor cells prevents histone acetylation, enhancer and promoter ...
Source: Blood - March 11, 2010 Category: Hematology Authors: Li, X., Hu, X., Patel, B., Zhou, Z., Liang, S., Ybarra, R., Qiu, Y., Felsenfeld, G., Bungert, J., Huang, S. Tags: Red Cells, Iron, and Erythropoiesis Source Type: journals
Membrane remodeling during reticulocyte maturation
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The transition of reticulocytes into erythrocytes is accompanied by extensive changes in the structure and properties of the plasma membrane. These changes include an increase in shear resistance, loss of surface area, and acquisition of a biconcave shape. The processes by which these changes are effected have remained largely undefined. Here we examine how the expression of 30 distinct membrane proteins and their interactions change during murine reticulocyte maturation. We show that tubulin and cytosolic actin are lost, whereas the membrane content of myosin, tropomyosin, intercellular adhesion molecule-4, glucose transp...
Source: Blood - March 11, 2010 Category: Hematology Authors: Liu, J., Guo, X., Mohandas, N., Chasis, J. A., An, X. Tags: Red Cells, Iron, and Erythropoiesis Source Type: journals
Placenta growth factor in sickle cell disease: association with hemolysis and inflammation
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Placenta growth factor (PlGF) is released by immature erythrocytes and is elevated in sickle cell disease (SCD). Previous data generated in vitro suggest that PlGF may play a role in the pathophysiology of SCD-associated pulmonary hypertension (PHT) by inducing the release of the vasoconstrictor, endothelin-1. In this cross-sectional study of 74 patients with SCD, we confirm that PlGF is significantly elevated in SCD compared with healthy control subjects. We found significantly higher levels of PlGF in SCD patients with PHT but observed no association of PlGF with the frequency of acute pain episodes or history of acute c...
Source: Blood - March 11, 2010 Category: Hematology Authors: Brittain, J. E., Hulkower, B., Jones, S. K., Strayhorn, D., De Castro, L., Telen, M. J., Orringer, E. P., Hinderliter, A., Ataga, K. I. Tags: Red Cells, Iron, and Erythropoiesis, Clinical Trials and Observations Source Type: journals
Deletion of the p110{beta} isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo
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During platelet activation, phosphoinositide 3-kinases (PI3Ks) produce lipid second messengers participating in the regulation of functional responses. Here, we generated a megakaryocyte-restricted p110β null mouse model and demonstrated a critical role of PI3Kβ in platelet activation via an immunoreceptor tyrosine-based activation motif, the glyco-protein VI-Fc receptor -chain complex, and its contribution in response to G-protein–coupled receptors. Interestingly, the production of phosphatidylinositol 3,4,5-trisphosphate and the activation of protein kinase B/Akt were strongly inhibited in p110β null...
Source: Blood - March 11, 2010 Category: Hematology Authors: Martin, V., Guillermet-Guibert, J., Chicanne, G., Cabou, C., Jandrot-Perrus, M., Plantavid, M., Vanhaesebroeck, B., Payrastre, B., Gratacap, M.-P. Tags: Platelets and Thrombopoiesis, Brief Reports Source Type: journals
Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms
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Somatic mutations in TET2 occur in patients with myeloproliferative neoplasms and other hematologic malignancies. It has been suggested that TET2 is a tumor suppressor gene and mutations in TET2 precede the acquisition of JAK2-V617F. To examine the order of events, we performed colony assays and genotyped TET2 and JAK2 in individual colonies. In 4 of 8 myeloproliferative neoplasm patients, we found that some colonies with mutated TET2 carried wild-type JAK2, whereas others were JAK2-V617F positive, indicating that TET2 occurred before JAK2-V617F. One of these patients carried a germline TET2 mutation. However, in 2 other p...
Source: Blood - March 11, 2010 Category: Hematology Authors: Schaub, F. X., Looser, R., Li, S., Hao-Shen, H., Lehmann, T., Tichelli, A., Skoda, R. C. Tags: Myeloid Neoplasia, Brief Reports Source Type: journals
Identification of DJ-1/PARK-7 as a determinant of stroma-dependent and TNF-{alpha}-induced apoptosis in MDS using mass spectrometry and phosphopeptide analysis
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In patients with myelodysplastic syndromes (MDS), apoptosis in hematopoietic cells is up-regulated in low-grade disease, whereas advanced disease is characterized by apoptosis resistance. We have shown that marrow stroma–derived signals convey sensitivity to tumor-necrosis-factor alpha (TNF-)–mediated apoptosis in otherwise-resistant KG1a myeloid cells and CD34+ cells from MDS marrow. Here, we used a PhosphoScan proteomic liquid chromatography–mass spectrometry method to identify signals relevant for this effect. The transcription factor DJ-1/PARK-7 (DJ-1) was highly phosphorylated in KG1a cells cultured ...
Source: Blood - March 11, 2010 Category: Hematology Authors: Marcondes, A. M., Li, X., Gooley, T. A., Milless, B., Deeg, H. J. Tags: Myeloid Neoplasia Source Type: journals
Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification
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Acute erythroid leukemia (AEL) is a rare type of acute myeloid leukemia (AML) for which diagnostic criteria have been refined in the 2008 World Health Organization (WHO) classification of AML. The relationship of AEL to myelodysplastic syndromes (MDSs) and to AML with myelodysplasia-related changes (AML-MRC) is not clearly defined. We conducted a retrospective, multi-institutional study of patients with AEL and compared them with patients with MDS or AML-MRC with erythroid hyperplasia (≥ 50% erythroid cells). Among a total of 124 patients with AEL, 32% had a history of MDS or chronic cytopenia, 32% had therapy-related d...
Source: Blood - March 11, 2010 Category: Hematology Authors: Hasserjian, R. P., Zuo, Z., Garcia, C., Tang, G., Kasyan, A., Luthra, R., Abruzzo, L. V., Kantarjian, H. M., Medeiros, L. J., Wang, S. A. Tags: Free Research Articles, Myeloid Neoplasia, Clinical Trials and Observations Source Type: journals
Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34- fraction
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Leukemia-initiating cells (LICs) in acute myeloid leukemia (AML) are believed to be restricted to the CD34+ fraction. However, one of the most frequently mutated genes in AML is nucleophosmin (NPM), and this is associated with low CD34 expression. We, therefore, investigated whether NPM-mutated AMLs have LICs restricted to the CD34+ fraction. We transplanted sorted fractions of primary NPM-mutated AML into immunodeficient mice to establish which fractions initiate leukemia. Approximately one-half of cases had LICs exclusively within the CD34– fraction, whereas the CD34+ fraction contained normal multilineage hematopo...
Source: Blood - March 11, 2010 Category: Hematology Authors: Taussig, D. C., Vargaftig, J., Miraki-Moud, F., Griessinger, E., Sharrock, K., Luke, T., Lillington, D., Oakervee, H., Cavenagh, J., Agrawal, S. G., Lister, T. A., Gribben, J. G., Bonnet, D. Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia Source Type: journals
