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B-cell acute lymphoblastic leukemia in JAK2 V617F-positive polycythemia vera
(Source: Blood)
Source: Blood - February 22, 2018 Category: Hematology Authors: Jaitly, V., Wang, W. Tags: Free Research Articles, BloodWork, Myeloid Neoplasia BLOOD WORK Source Type: research

Chewing the bone: bone marrow with adult T-cell leukemia/lymphoma
(Source: Blood)
Source: Blood - February 22, 2018 Category: Hematology Authors: Siref, A., Huang, Q. Tags: Free Research Articles, BloodWork, Lymphoid Neoplasia BLOOD WORK Source Type: research

Identification of novel recurrent STAT3-RARA fusions in acute promyelocytic leukemia lacking t(15;17)(q22;q12)/PML-RARA
(Source: Blood)
Source: Blood - February 22, 2018 Category: Hematology Authors: Yao, L., Wen, L., Wang, N., Liu, T., Xu, Y., Ruan, C., Wu, D., Chen, S. Tags: Myeloid Neoplasia Letter to Blood Source Type: research

Intraocular involvement of mycosis fungoides associated with immunophenotypic switch from CD4+ to CD8+
(Source: Blood)
Source: Blood - February 22, 2018 Category: Hematology Authors: Braue, J. A., Daniels, A. B., Zwerner, J. P., Kim, S. J., Zic, J. A. Tags: Lymphoid Neoplasia Letter to Blood Source Type: research

Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency
The primary immunodeficiencies (PIDs), rare inherited diseases characterized by severe dysfunction of immunity, have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in childhood. Controversy exists regarding optimal timing and use of Allo-HSCT in adults, due to lack of experience and previous poor outcomes. Twenty-nine consecutive adult patients, with a mean age at transplant of 24 years (range, 17-50 years), underwent Allo-HSCT. Reduced-intensity conditioning (RIC) included fludarabine (Flu)/melphalan/alemtuzumab (n = 20), Flu/busulfan (Bu)/alemtuzumab (n = 8), and Flu/Bu/antith...
Source: Blood - February 22, 2018 Category: Hematology Authors: Fox, T. A., Chakraverty, R., Burns, S., Carpenter, B., Thomson, K., Lowe, D., Fielding, A., Peggs, K., Kottaridis, P., Uttenthal, B., Bigley, V., Buckland, M., Grandage, V., Denovan, S., Grace, S., Dahlstrom, J., Workman, S., Symes, A., Mackinnon, S., Hou Tags: Immunobiology and Immunotherapy, Transplantation, Free Research Articles, Clinical Trials and Observations Source Type: research

A novel role for the macrophage galactose-type lectin receptor in mediating von Willebrand factor clearance
In this study, we investigated (1) the specific importance of N- vs O-linked sialic acid in protecting against VWF clearance and (2) whether additional receptors contribute to the reduced half-life of hyposialylated VWF. α2-3-linked sialic acid accounts for
Source: Blood - February 22, 2018 Category: Hematology Authors: Ward, S. E., OSullivan, J. M., Drakeford, C., Aguila, S., Jondle, C. N., Sharma, J., Fallon, P. G., Brophy, T. M., Preston, R. J. S., Smyth, P., Sheils, O., Chion, A., ODonnell, J. S. Tags: Thrombosis and Hemostasis, Brief Reports Source Type: research

Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin
Nonclassical ferroportin disease (FD) is a form of hereditary hemochromatosis caused by mutations in the iron transporter ferroportin (Fpn), resulting in parenchymal iron overload. Fpn is regulated by the hormone hepcidin, which induces Fpn endocytosis and cellular iron retention. We characterized 11 clinically relevant and 5 nonclinical Fpn mutations using stably transfected, inducible isogenic cell lines. All clinical mutants were functionally resistant to hepcidin as a consequence of either impaired hepcidin binding or impaired hepcidin-dependent ubiquitination despite intact hepcidin binding. Mapping the residues onto ...
Source: Blood - February 22, 2018 Category: Hematology Authors: Aschemeyer, S., Qiao, B., Stefanova, D., Valore, E. V., Sek, A. C., Ruwe, T. A., Vieth, K. R., Jung, G., Casu, C., Rivella, S., Jormakka, M., Mackenzie, B., Ganz, T., Nemeth, E. Tags: Red Cells, Iron, and Erythropoiesis Source Type: research

Activity of the PI3K-{delta},{gamma} inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma
Duvelisib (IPI-145) is an oral inhibitor of phosphatidylinositol 3-kinase (PI3K)–/ isoforms currently in clinical development. PI3K-/ inhibition may directly inhibit malignant T-cell growth, making duvelisib a promising candidate for patients with peripheral (PTCL) or cutaneous (CTCL) T-cell lymphoma. Inhibition of either isoform may also contribute to clinical responses by modulating nonmalignant immune cells. We investigated these dual effects in a TCL cohort from a phase 1, open-label study of duvelisib in patients with relapsed or refractory PTCL (n = 16) and CTCL (n = 19), along with in vitro and in vivo models ...
Source: Blood - February 22, 2018 Category: Hematology Authors: Horwitz, S. M., Koch, R., Porcu, P., Oki, Y., Moskowitz, A., Perez, M., Myskowski, P., Officer, A., Jaffe, J. D., Morrow, S. N., Allen, K., Douglas, M., Stern, H., Sweeney, J., Kelly, P., Kelly, V., Aster, J. C., Weaver, D., Foss, F. M., Weinstock, D. M. Tags: Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

Duvelisib, a novel oral dual inhibitor of PI3K-{delta},{gamma}, is clinically active in advanced hematologic malignancies
Duvelisib is an oral dual inhibitor of phosphoinositide 3-kinase- (PI3K-) and PI3K- in late-stage clinical development for hematologic malignancy treatment. This phase 1 study evaluated maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics (PD), efficacy, and safety of duvelisib in 210 patients with advanced hematologic malignancies. In the dose escalation phase (n = 31), duvelisib 8 to 100 mg twice daily was administered, with MTD determined as 75 mg twice daily. In the expansion phase (n = 179), patients with indolent non-Hodgkin lymphoma (iNHL), chronic lymphocytic leukemia (CLL), or T-cell lymphoma (TCL) wer...
Source: Blood - February 22, 2018 Category: Hematology Authors: Flinn, I. W., OBrien, S., Kahl, B., Patel, M., Oki, Y., Foss, F. F., Porcu, P., Jones, J., Burger, J. A., Jain, N., Kelly, V. M., Allen, K., Douglas, M., Sweeney, J., Kelly, P., Horwitz, S. Tags: Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

Platelet glycoprotein VI aids in local immunity during pneumonia-derived sepsis caused by gram-negative bacteria
Platelet collagen receptor glycoprotein VI (GPVI) and podoplanin receptor C-type lectin-like receptor 2 (CLEC2) are receptors implicated in platelet activation that both signal via an immunoreceptor tyrosine–based activation motif. Platelets are necessary for host defense and prevention of hemorrhage during sepsis, but the role of platelet GPVI and CLEC2 herein is unknown. To investigate this, we infected mice depleted of platelet GPVI or CLEC2 by antibody treatment or GPVI–/– mice with the common human sepsis pathogen Klebsiella pneumoniae via the airways to induce pneumonia-derived sepsis. The GPVI liga...
Source: Blood - February 22, 2018 Category: Hematology Authors: Claushuis, T. A. M., de Vos, A. F., Nieswandt, B., Boon, L., Roelofs, J. J. T. H., de Boer, O. J., van t Veer, C., van der Poll, T. Tags: Immunobiology and Immunotherapy, Platelets and Thrombopoiesis Source Type: research

Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia
Novel therapies are needed for patients with relapsed or refractory multiple myeloma (MM). We conducted a multicenter, phase 1 study in advanced hematological malignancies to assess the safety, efficacy, and recommended phase 2 dose (RP2D) of oral selinexor, a selective inhibitor of the nuclear export protein XPO1. In the dose-escalation phase, 25 patients with heavily pretreated MM (22) or Waldenstrom macroglobulinemia (3) were administered selinexor (3-60 mg/m2) in 8 or 10 doses per 28-day cycle. In the dose-expansion phase, 59 patients with MM received selinexor at 45 or 60 mg/m2 with 20 mg dexamethasone, twice weekly i...
Source: Blood - February 22, 2018 Category: Hematology Authors: Chen, C., Siegel, D., Gutierrez, M., Jacoby, M., Hofmeister, C. C., Gabrail, N., Baz, R., Mau-Sorensen, M., Berdeja, J. G., Savona, M., Savoie, L., Trudel, S., Areethamsirikul, N., Unger, T. J., Rashal, T., Hanke, T., Kauffman, M., Shacham, S., Reece, D. Tags: Multiple Myeloma, Free Research Articles, Myeloid Neoplasia, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research

How I treat disseminated intravascular coagulation
Disseminated intravascular coagulation (DIC) is a condition characterized by systemic activation of coagulation, potentially leading to thrombotic obstruction of small and midsize vessels, thereby contributing to organ dysfunction. At the same time, ongoing consumption of platelets and coagulation proteins results in thrombocytopenia and low concentrations of clotting factors, which may cause profuse hemorrhagic complications. DIC is always secondary to an underlying condition, such as severe infections, solid or hematologic malignancies, trauma, or obstetric calamities. A reliable diagnosis of DIC can be made through simp...
Source: Blood - February 22, 2018 Category: Hematology Authors: Levi, M., Scully, M. Tags: Transfusion Medicine, How I Treat, Free Research Articles, Thrombosis and Hemostasis Source Type: research

HSCT for PID: not just for children
(Source: Blood)
Source: Blood - February 22, 2018 Category: Hematology Authors: Davila Saldana, B. J. Tags: Free Research Articles COMMENTS Source Type: research

VWF clearance: its glycomplicated
(Source: Blood)
Source: Blood - February 22, 2018 Category: Hematology Authors: Denis, C. V., Lenting, P. J. Tags: Free Research Articles COMMENTS Source Type: research

How does hepcidin hinder ferroportin activity?
(Source: Blood)
Source: Blood - February 22, 2018 Category: Hematology Authors: Zhang, D.-L., Rouault, T. A. Tags: Free Research Articles COMMENTS Source Type: research

Dual PI3K blockade: PTCLs Achilles heel?
(Source: Blood)
Source: Blood - February 22, 2018 Category: Hematology Authors: Brammer, J. E. Tags: Free Research Articles COMMENTS Source Type: research

Genetic landscape of inherited BMF
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Tags: Free Research Articles, CME article CONTINUING MEDICAL EDUCATION (CME) QUESTIONS Source Type: research

Jordans anomaly
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Winokur, D., LiPera, W. Tags: Free Research Articles, BloodWork, Phagocytes, Granulocytes, and Myelopoiesis BLOOD WORK Source Type: research

When it rains, it pours
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Degaud, M., Sujobert, P. Tags: Free Research Articles, BloodWork, Lymphoid Neoplasia BLOOD WORK Source Type: research

ABO zygosity, but not secretor or Fc receptor status, is a significant risk factor for IVIG-associated hemolysis
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Branch, D. R., Hellberg, A., Bruggeman, C. W., Storry, J. R., Sakac, D., Blacquiere, M., Tong, T. N., Burke-Murphy, E., Binnington, B., Parmar, N., Riden, L. S., Willie, K., Armali, C., Aziz, J., Lieberman, L., Laroche, V., Callum, J., Lin, Y., Shehata, N Tags: Transfusion Medicine Letter to Blood Source Type: research

Loss of RKIP is a frequent event in myeloid sarcoma and promotes leukemic tissue infiltration
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Caraffini, V., Perfler, B., Berg, J. L., Uhl, B., Schauer, S., Kashofer, K., Ghaffari-Tabrizi-Wizsy, N., Strobl, H., Wölfler, A., Hoefler, G., Sill, H., Zebisch, A. Tags: Myeloid Neoplasia Letter to Blood Source Type: research

Five percent of healthy newborns have an ETV6-RUNX1 fusion as revealed by DNA-based GIPFEL screening
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Schäfer, D., Olsen, M., Lähnemann, D., Stanulla, M., Slany, R., Schmiegelow, K., Borkhardt, A., Fischer, U. Tags: Pediatric Hematology, Lymphoid Neoplasia Letter to Blood Source Type: research

Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Zeidan, A. M., Stahl, M., Hu, X., Wang, R., Huntington, S. F., Podoltsev, N. A., Gore, S. D., Ma, X., Davidoff, A. J. Tags: Myeloid Neoplasia, Clinical Trials and Observations Letter to Blood Source Type: research

Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation
HLA-DPB1 T-cell epitope (TCE) mismatching algorithm and rs9277534 SNP at the 3' untranslated region (3'UTR) in the HLA-DPB1 gene are key factors for transplant-related events in unrelated hematopoietic cell transplantation (UR-HCT). However, the association of these 2 mechanisms has not been elucidated. We analyzed 19 frequent HLA-DPB1 alleles derived from Japanese healthy subjects by next-generation sequencing of the entire HLA-DPB1 gene region and multi-SNP data of the HLA region in 1589 UR-HCT pairs. The risk of acute graft-versus-host disease (aGVHD) was analyzed in 1286 patients with single HLA-DPB1 mismatch UR-HCT. T...
Source: Blood - February 15, 2018 Category: Hematology Authors: Morishima, S., Shiina, T., Suzuki, S., Ogawa, S., Sato-Otsubo, A., Kashiwase, K., Azuma, F., Yabe, T., Satake, M., Kato, S., Kodera, Y., Sasazuki, T., Morishima, Y., for the Japan Marrow Donor Program Tags: Transplantation Source Type: research

Altered plasma clot properties increase the risk of recurrent deep vein thrombosis: a cohort study
It has been demonstrated that fibrin clots generated from plasma samples obtained from patients with prior thromboembolic events are denser and less susceptible to lysis. Such a prothrombotic fibrin clot phenotype has been suggested as a new risk factor for venous thromboembolism, but its prognostic value is unclear. To assess whether abnormal clot properties can predict recurrent deep vein thrombosis (DVT), we studied 320 consecutive patients aged 18 to 70 years following the first-ever DVT. Plasma clot properties were evaluated after 3 months of anticoagulant treatment since the index event. A mean duration of anticoagul...
Source: Blood - February 15, 2018 Category: Hematology Authors: Cieslik, J., Mrozinska, S., Broniatowska, E., Undas, A. Tags: Thrombosis and Hemostasis Source Type: research

Fc-independent immune thrombocytopenia via mechanomolecular signaling in platelets
Immune thrombocytopenia (ITP) is a prevalent autoimmune disease characterized by autoantibody-induced platelet clearance. Some ITP patients are refractory to standard immunosuppressive treatments such as intravenous immunoglobulin (IVIg). These patients often have autoantibodies that target the ligand-binding domain (LBD) of glycoprotein Ibα (GPIbα), a major subunit of the platelet mechanoreceptor complex GPIb-IX. However, the molecular mechanism of this Fc-independent platelet clearance is not clear. Here, we report that many anti-LBD monoclonal antibodies such as 6B4, but not AK2, activated GPIb-IX in a shear...
Source: Blood - February 15, 2018 Category: Hematology Authors: Quach, M. E., Dragovich, M. A., Chen, W., Syed, A. K., Cao, W., Liang, X., Deng, W., De Meyer, S. F., Zhu, G., Peng, J., Ni, H., Bennett, C. M., Hou, M., Ware, J., Deckmyn, H., Zhang, X. F., Li, R. Tags: Thrombocytopenia, Platelets and Thrombopoiesis Source Type: research

Defining the requirements for the pathogenic interaction between mutant calreticulin and MPL in MPN
Mutations in calreticulin (CALR) are phenotypic drivers in the pathogenesis of myeloproliferative neoplasms. Mechanistic studies have demonstrated that mutant CALR binds to the thrombopoietin receptor MPL, and that the positive electrostatic charge of the mutant CALR C terminus is required for mutant CALR-mediated activation of JAK-STAT signaling. Here we demonstrate that although binding between mutant CALR and MPL is required for mutant CALR to transform hematopoietic cells; binding alone is insufficient for cytokine independent growth. We further show that the threshold of positive charge in the mutant CALR C terminus i...
Source: Blood - February 15, 2018 Category: Hematology Authors: Elf, S., Abdelfattah, N. S., Baral, A. J., Beeson, D., Rivera, J. F., Ko, A., Florescu, N., Birrane, G., Chen, E., Mullally, A. Tags: Myeloid Neoplasia, Brief Reports Source Type: research

Diminished microRNA-29b level is associated with BRD4-mediated activation of oncogenes in cutaneous T-cell lymphoma
In this study, we characterize a novel miR dysregulation that contributes to overexpression of the epigenetic reader bromodomain-containing protein 4 (BRD4). We used patient CD4+ T cells to show diminished levels of miR-29b compared with healthy donor cells. Patient cells and miR-29b–/– mouse cells revealed an inverse relationship between miR-29b and BRD4, the latter of which is overexpressed in these cells. Chromatin immunoprecipitation and sequencing analysis revealed increased genome-wide BRD4 occupancy at promoter and enhancer regions in CD4+ T cells from CTCL patients. The cumulative result of BRD4 binding...
Source: Blood - February 15, 2018 Category: Hematology Authors: Kohnken, R., Wen, J., Mundy-Bosse, B., McConnell, K., Keiter, A., Grinshpun, L., Hartlage, A., Yano, M., McNeil, B., Chakravarti, N., William, B., Bradner, J. E., Caligiuri, M. A., Porcu, P., Mishra, A. Tags: Lymphoid Neoplasia Source Type: research

Prognostic miRNA classifier in early-stage mycosis fungoides: development and validation in a Danish nationwide study
Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma. The disease often takes an indolent course, but in approximately one-third of the patients, the disease progresses to an aggressive malignancy with a poor prognosis. At the time of diagnosis, it is impossible to predict which patients develop severe disease and are in need of aggressive treatment. Accordingly, we investigated the prognostic potential of microRNAs (miRNAs) at the time of diagnosis in MF. Using a quantitative reverse transcription polymerase chain reaction platform, we analyzed miRNA expression in diagnostic skin biopsies from 154...
Source: Blood - February 15, 2018 Category: Hematology Authors: Lindahl, L. M., Besenbacher, S., Rittig, A. H., Celis, P., Willerslev-Olsen, A., Gjerdrum, L. M. R., Krejsgaard, T., Johansen, C., Litman, T., Woetmann, A., Odum, N., Iversen, L. Tags: Free Research Articles, Lymphoid Neoplasia Source Type: research

An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma
B-cell maturation antigen (BCMA) is a promising therapeutic target for multiple myeloma (MM), but expression is variable, and early reports of BCMA targeting chimeric antigen receptors (CARs) suggest antigen downregulation at relapse. Dual-antigen targeting increases targetable tumor antigens and reduces the risk of antigen-negative disease escape. "A proliferation-inducing ligand" (APRIL) is a natural high-affinity ligand for BCMA and transmembrane activator and calcium-modulator and cyclophilin ligand (TACI). We quantified surface tumor expression of BCMA and TACI on primary MM cells (n = 50). All cases tested ...
Source: Blood - February 15, 2018 Category: Hematology Authors: Lee, L., Draper, B., Chaplin, N., Philip, B., Chin, M., Galas-Filipowicz, D., Onuoha, S., Thomas, S., Baldan, V., Bughda, R., Maciocia, P., Kokalaki, E., Neves, M. P., Patel, D., Rodriguez-Justo, M., Francis, J., Yong, K., Pule, M. Tags: Multiple Myeloma, Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research

Copper 64-labeled daratumumab as a PET/CT imaging tracer for multiple myeloma
As a growing number of patients with multiple myeloma (MM) respond to upfront therapies while eventually relapsing in a time frame that is often unpredictable, attention has increasingly focused on developing novel diagnostic criteria to also account for disease dissemination. Positron emission tomography/computed tomography (PET/CT) is often used as a noninvasive monitoring strategy to assess cancer cell dissemination, but because the uptake of the currently used radiotracer 18fluorodeoxyglucose (18F-FDG) is a function of the metabolic activity of both malignant and nonmalignant cells, the results frequently lack sufficie...
Source: Blood - February 15, 2018 Category: Hematology Authors: Caserta, E., Chea, J., Minnix, M., Viola, D., Vonderfecht, S., Yazaki, P., Crow, D., Khalife, J., Sanchez, J. F., Palmer, J. M., Hui, S., Carlesso, N., Keats, J., Kim, Y., Buettner, R., Marcucci, G., Rosen, S., Shively, J., Colcher, D., Krishnan, A., Pich Tags: Immunobiology and Immunotherapy, Brief Reports Source Type: research

How I use catheter-directed interventional therapy to treat patients with venous thromboembolism
Patients who present with severe manifestations of acute venous thromboembolism (VTE) are at higher risk for premature death and long-term disability. In recent years, catheter-based interventional procedures have shown strong potential to improve clinical outcomes in selected VTE patients. However, physicians continue to be routinely faced with challenging decisions that pertain to the utilization of these risky and costly treatment strategies, and there is a relative paucity of published clinical trials with sufficient rigor and directness to inform clinical practice. In this article, using 3 distinct clinical scenario p...
Source: Blood - February 15, 2018 Category: Hematology Authors: Vedantham, S., Sista, A. K. Tags: How I Treat, Free Research Articles, Thrombosis and Hemostasis Source Type: research

A landscape of germ line mutations in a cohort of inherited bone marrow failure patients
This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling. (Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Bluteau, O., Sebert, M., Leblanc, T., Peffault de Latour, R., Quentin, S., Lainey, E., Hernandez, L., Dalle, J.-H., Sicre de Fontbrune, F., Lengline, E., Itzykson, R., Clappier, E., Boissel, N., Vasquez, N., Da Costa, M., Masliah-Planchon, J., Cuccuini, W Tags: Hematopoiesis and Stem Cells, Pediatric Hematology, Plenary Papers, Free Research Articles, Myeloid Neoplasia, Red Cells, Iron, and Erythropoiesis, CME article, Clinical Trials and Observations Source Type: research

Clot structure predicts recurrent thrombosis
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: White, N. J. Tags: Free Research Articles COMMENTS Source Type: research

Only the strong: when antibodies hold on
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Thomas, W. E. Tags: Free Research Articles COMMENTS Source Type: research

BRD4: epigenetic origin and target of CTCL
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Zhao, X., Tao, J. Tags: Free Research Articles COMMENTS Source Type: research

Distinct miRNA profile in prognosis of early CTCL
(Source: Blood)
Source: Blood - February 15, 2018 Category: Hematology Authors: Wasik, M. A. Tags: Free Research Articles COMMENTS Source Type: research

Martin-Pardillos A, Tsaalbi-Shtylik A, Chen S, et al. Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions. Blood. 2017;130(13):1523-1534.
(Source: Blood)
Source: Blood - February 8, 2018 Category: Hematology Tags: Free Research Articles ERRATA Source Type: research

Wong RSM, Saleh MN, Khelif A, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130(23):2527-2536.
(Source: Blood)
Source: Blood - February 8, 2018 Category: Hematology Tags: Free Research Articles ERRATA Source Type: research

Interference of hyperleukocytosis in red blood cell count
(Source: Blood)
Source: Blood - February 8, 2018 Category: Hematology Authors: Favre, R., Genthon, A. Tags: Free Research Articles, BloodWork, Red Cells, Iron, and Erythropoiesis BLOOD WORK Source Type: research

Syphilitic lymphadenitis with abscess formation involving cervical lymph nodes
(Source: Blood)
Source: Blood - February 8, 2018 Category: Hematology Authors: Duffield, A. S., Borowitz, M. J. Tags: Free Research Articles, BloodWork, Clinical Trials and Observations BLOOD WORK Source Type: research

Normal plasma IgG inhibits HIT antibody-mediated platelet activation: implications for therapeutic plasma exchange
(Source: Blood)
Source: Blood - February 8, 2018 Category: Hematology Authors: Jones, C. G., Pechauer, S. M., Curtis, B. R., Bougie, D. W., Aster, R. H., Padmanabhan, A. Tags: Thrombocytopenia, Transfusion Medicine, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Letter to Blood Source Type: research

Adaptive reprogramming of NK cells in X-linked lymphoproliferative syndrome
(Source: Blood)
Source: Blood - February 8, 2018 Category: Hematology Authors: Opat, S., Hearps, A. C., Thia, K., Yuen, A., Rogers, B., Chachage, M., Moore, G., Shortt, J., Ryland, G., Blombery, P., Schwarer, A. P., Noori, T., Trapani, J. A., Jaworowski, A., Voskoboinik, I. Tags: Pediatric Hematology, Immunobiology and Immunotherapy Letter to Blood Source Type: research

Myosin IIa is critical for cAMP-mediated endothelial secretion of von Willebrand factor
Nonmuscle myosin II has been implicated in regulation of von Willebrand factor (VWF) release from endothelial Weibel-Palade bodies (WPBs), but the specific role of myosin IIa isoform is poorly defined. Here, we report that myosin IIa is expressed both in primary human endothelial cells and intact mouse vessels, essential for cyclic adenosine monophosphate (cAMP)-mediated endothelial VWF secretion. Downregulation of myosin IIa by shRNAs significantly suppressed both forskolin- and epinephrine-induced VWF secretion. Endothelium-specific myosin IIa knockout mice exhibited impaired epinephrine-stimulated VWF release, prolonged...
Source: Blood - February 8, 2018 Category: Hematology Authors: Li, P., Wei, G., Cao, Y., Deng, Q., Han, X., Huang, X., Huo, Y., He, Y., Chen, L., Luo, J. Tags: Thrombosis and Hemostasis, Vascular Biology Source Type: research

Identification of the integrin-binding site on coagulation factor VIIa required for proangiogenic PAR2 signaling
The tissue factor (TF) pathway serves both hemostasis and cell signaling, but how cells control these divergent functions of TF remains incompletely understood. TF is the receptor and scaffold of coagulation proteases cleaving protease-activated receptor 2 (PAR2) that plays pivotal roles in angiogenesis and tumor development. Here we demonstrate that coagulation factor VIIa (FVIIa) elicits TF cytoplasmic domain-dependent proangiogenic cell signaling independent of the alternative PAR2 activator matriptase. We identify a Lys-Gly-Glu (KGE) integrin-binding motif in the FVIIa protease domain that is required for association o...
Source: Blood - February 8, 2018 Category: Hematology Authors: Rothmeier, A. S., Liu, E., Chakrabarty, S., Disse, J., Mueller, B. M., Ostergaard, H., Ruf, W. Tags: Thrombosis and Hemostasis, Vascular Biology Source Type: research

The interaction of ENL with PAF1 mitigates polycomb silencing and facilitates murine leukemogenesis
Eleven-nineteen leukemia (ENL) is a chromatin reader present in complexes stimulating transcriptional elongation. It is fused to mixed-lineage leukemia (MLL) in leukemia, and missense mutations have been identified in Wilms tumor and acute myeloid leukemia. Here we demonstrate that ENL overcomes polycomb silencing through recruitment of PAF1 via the conserved YEATS domain, which recognizes acetylated histone H3. PAF1 was responsible for antirepressive activities of ENL in vitro, and it determined the transforming potential of MLL-ENL. MLL-ENL target loci showed supraphysiological PAF1 binding, hyperubiquitination of histon...
Source: Blood - February 8, 2018 Category: Hematology Authors: Hetzner, K., Garcia-Cuellar, M.-P., Büttner, C., Slany, R. K. Tags: Myeloid Neoplasia Source Type: research

Mutant calreticulin knockin mice develop thrombocytosis and myelofibrosis without a stem cell self-renewal advantage
In this study, we generated a conditional mouse knockin model of the most common CALR mutation, a 52-bp deletion. The mutant novel human C-terminal sequence is integrated into the otherwise intact mouse CALR gene and results in mutant CALR expression under the control of the endogenous mouse locus. CALRdel/+ mice develop a transplantable ET-like disease with marked thrombocytosis, which is associated with increased and morphologically abnormal megakaryocytes and increased numbers of phenotypically defined hematopoietic stem cells (HSCs). Homozygous CALRdel/del mice developed extreme thrombocytosis accompanied by features o...
Source: Blood - February 8, 2018 Category: Hematology Authors: Li, J., Prins, D., Park, H. J., Grinfeld, J., Gonzalez-Arias, C., Loughran, S., Dovey, O. M., Klampfl, T., Bennett, C., Hamilton, T. L., Pask, D. C., Sneade, R., Williams, M., Aungier, J., Ghevaert, C., Vassiliou, G. S., Kent, D. G., Green, A. R. Tags: Myeloid Neoplasia Source Type: research

Pml nuclear body disruption cooperates in APL pathogenesis and impairs DNA damage repair pathways in mice
A hallmark of acute promyelocytic leukemia (APL) is altered nuclear architecture, with disruption of promyelocytic leukemia (PML) nuclear bodies (NBs) mediated by the PML–retinoic acid receptor α (RARα) oncoprotein. To address whether this phenomenon plays a role in disease pathogenesis, we generated a knock-in mouse model with NB disruption mediated by 2 point mutations (C62A/C65A) in the Pml RING domain. Although no leukemias developed in PmlC62A/C65A mice, these transgenic mice also expressing RARα linked to a dimerization domain (p50-RARα model) exhibited a doubling in the rate of leukemia...
Source: Blood - February 8, 2018 Category: Hematology Authors: Voisset, E., Moravcsik, E., Stratford, E. W., Jaye, A., Palgrave, C. J., Hills, R. K., Salomoni, P., Kogan, S. C., Solomon, E., Grimwade, D. Tags: Myeloid Neoplasia Source Type: research

Physiological Srsf2 P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice
Splicing factor mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not been fully elucidated. In the present study, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre–mediated conditional knockin mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplantation settings. Srsf2-mutated hematopoiet...
Source: Blood - February 8, 2018 Category: Hematology Authors: Kon, A., Yamazaki, S., Nannya, Y., Kataoka, K., Ota, Y., Nakagawa, M. M., Yoshida, K., Shiozawa, Y., Morita, M., Yoshizato, T., Sanada, M., Nakayama, M., Koseki, H., Nakauchi, H., Ogawa, S. Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia Source Type: research

CD38-bispecific antibody pretargeted radioimmunotherapy for multiple myeloma and other B-cell malignancies
We describe a new PRIT approach for the treatment of multiple myeloma (MM) and other B-cell malignancies, for which we developed an anti-CD38–bispecific fusion protein that eliminates endogenous biotin interference and immunogenic elements. In murine xenograft models of MM and non-Hodgkin lymphoma (NHL), the CD38-bispecific construct demonstrated excellent blood clearance and tumor targeting. Dosimetry calculations showed a tumor-absorbed dose of 43.8 Gy per millicurie injected dose of 90Y, with tumor-to-normal organ dose ratios of 7:1 for liver and 15:1 for lung and kidney. In therapy studies, CD38-bispecific PRIT r...
Source: Blood - February 8, 2018 Category: Hematology Authors: Green, D. J., OSteen, S., Lin, Y., Comstock, M. L., Kenoyer, A. L., Hamlin, D. K., Wilbur, D. S., Fisher, D. R., Nartea, M., Hylarides, M. D., Gopal, A. K., Gooley, T. A., Orozco, J. J., Till, B. G., Orcutt, K. D., Wittrup, K. D., Press, O. W. Tags: Multiple Myeloma, Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research