Leukemic-phase progression of aleukemic mast cell leukemia
(Source: Blood)
Source: Blood - May 24, 2018 Category: Hematology Authors: Patel, S. S., Dorfman, D. M. Tags: Free Research Articles, BloodWork, Myeloid Neoplasia BLOOD WORK Source Type: research

Germ line tissues for optimal detection of somatic variants in myelodysplastic syndromes
(Source: Blood)
Source: Blood - May 24, 2018 Category: Hematology Authors: Padron, E., Ball, M. C., Teer, J. K., Painter, J. S., Yoder, S. J., Zhang, C., Zhang, L., Moscinski, L. C., Rollison, D. E., Gore, S. D., Bejar, R., Walter, M. J., Sekeres, M. A., Komrokji, R. S., Epling-Burnette, P. K. Tags: Myeloid Neoplasia Letter to Blood Source Type: research

Eltrombopag mobilizes iron in patients with aplastic anemia
(Source: Blood)
Source: Blood - May 24, 2018 Category: Hematology Authors: Zhao, Z., Sun, Q., Sokoll, L. J., Streiff, M., Cheng, Z., Grasmeder, S., Townsley, D. M., Young, N. S., Dunbar, C. E., Winkler, T. Tags: Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis, Clinical Trials and Observations Letter to Blood Source Type: research

Donor telomere length and causes of death after unrelated hematopoietic cell transplantation in patients with marrow failure
This study aimed to determine whether cell-specific lymphocyte TL is associated with certain post-HCT causes of death. We used flow cytometry and fluorescence in situ hybridization to measure TL in donor total lymphocytes and subsets: naìˆve enriched T cells (CD45RA+CD20–), memory enriched T cells (CD45RA–CD20–), natural killer (NK) fully differentiated T cells (CD45RA+CD57+), and B cells (CD45RA+CD20+). Competing risk survival regression was used for cause-specific death analyses. Clinical data and biospecimens were available from the Center for International Blood and Marrow Transplant Research databas...
Source: Blood - May 24, 2018 Category: Hematology Authors: Gadalla, S. M., Aubert, G., Wang, T., Haagenson, M., Spellman, S. R., Wang, L., Katki, H. A., Savage, S. A., Lee, S. J. Tags: Hematopoiesis and Stem Cells, Transplantation Source Type: research

Factor VIIa induces anti-inflammatory signaling via EPCR and PAR1
Recent studies show that endothelial cell protein C receptor (EPCR) interacts with diverse ligands, in addition to its known ligands protein C and activated protein C (APC). We showed in earlier studies that procoagulant clotting factor VIIa (FVIIa) binds EPCR and downregulates EPCR-mediated anticoagulation and induces an endothelial barrier protective effect. Here, we investigated the effect of FVIIa’s interaction with EPCR on endothelial cell inflammation and lipopolysaccharide (LPS)-induced inflammatory responses in vivo. Treatment of endothelial cells with FVIIa suppressed tumor necrosis factor α (TNF-&alph...
Source: Blood - May 24, 2018 Category: Hematology Authors: Kondreddy, V., Wang, J., Keshava, S., Esmon, C. T., Rao, L. V. M., Pendurthi, U. R. Tags: Thrombosis and Hemostasis Source Type: research

NADPH oxidase activation regulates apoptotic neutrophil clearance by murine macrophages
The phagocyte reduced NAD phosphate (NADPH) oxidase generates superoxide, the precursor to reactive oxygen species (ROS) that has both antimicrobial and immunoregulatory functions. Inactivating mutations in NADPH oxidase alleles cause chronic granulomatous disease (CGD), characterized by enhanced susceptibility to life-threatening microbial infections and inflammatory disorders; hypomorphic NADPH oxidase alleles are associated with autoimmunity. Impaired apoptotic cell (AC) clearance is implicated as an important contributing factor in chronic inflammation and autoimmunity, but the role of NADPH oxidase–derived ROS i...
Source: Blood - May 24, 2018 Category: Hematology Authors: Bagaitkar, J., Huang, J., Zeng, M. Y., Pech, N. K., Monlish, D. A., Perez-Zapata, L. J., Miralda, I., Schuettpelz, L. G., Dinauer, M. C. Tags: Phagocytes, Granulocytes, and Myelopoiesis Source Type: research

Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study
The safety and efficacy of ibrutinib (420 mg) in chronic lymphocytic leukemia (CLL) were evaluated in a phase 2 study; 51 patients had TP53 aberration (TP53 cohort) and 35 were enrolled because of age 65 years or older (elderly cohort). Both cohorts included patients with treatment-naive (TN) and relapsed/refractory (RR) CLL. With the median follow-up of 4.8 years, 49 (57.0%) of 86 patients remain on study. Treatment was discontinued for progressive disease in 20 (23.3%) patients and for adverse events in 5 (5.8%). Atrial fibrillation occurred in 18 (20.9%) patients for a rate of 6.4 per 100 patient-years. No serious bleed...
Source: Blood - May 24, 2018 Category: Hematology Authors: Ahn, I. E., Farooqui, M. Z. H., Tian, X., Valdez, J., Sun, C., Soto, S., Lotter, J., Housel, S., Stetler-Stevenson, M., Yuan, C. M., Maric, I., Calvo, K. R., Nierman, P., Hughes, T. E., Saba, N. S., Marti, G. E., Pittaluga, S., Herman, S. E. M., Niemann, Tags: Lymphoid Neoplasia Source Type: research

Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma
In diffuse large B-cell lymphoma (DLBCL), activation of the B-cell receptor (BCR) promotes multiple oncogenic signals, which are essential for tumor proliferation. Inhibition of the Bruton’s tyrosine kinase (BTK), a BCR downstream target, is therapeutically effective only in a subgroup of patients with DLBCL. Here, we used lymphoma cells isolated from patients with DLBCL to measure the effects of targeted therapies on BCR signaling and to anticipate response. In lymphomas resistant to BTK inhibition, we show that blocking BTK activity enhanced tumor dependencies from alternative oncogenic signals downstream of the BC...
Source: Blood - May 24, 2018 Category: Hematology Authors: Battistello, E., Katanayeva, N., Dheilly, E., Tavernari, D., Donaldson, M. C., Bonsignore, L., Thome, M., Christie, A. L., Murakami, M. A., Michielin, O., Ciriello, G., Zoete, V., Oricchio, E. Tags: Lymphoid Neoplasia Source Type: research

Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
Integrity of the T-cell receptor/CD3 complex is crucial for positive and negative selection of T cells in the thymus and for effector and regulatory functions of peripheral T lymphocytes. In humans, CD3D, CD3E, and CD3Z gene defects are a cause of severe immune deficiency and present early in life with increased susceptibility to infections. By contrast, CD3G mutations lead to milder phenotypes, mainly characterized by autoimmunity. However, the role of CD3 in establishing and maintaining immune tolerance has not been elucidated. In this manuscript, we aimed to investigate abnormalities of T-cell repertoire and function in...
Source: Blood - May 24, 2018 Category: Hematology Authors: Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, Tags: Immunobiology and Immunotherapy Source Type: research

Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up
Anti-CD22 moxetumomab pasudotox achieved 46% complete remissions (CRs) in previously reported phase 1 testing in relapsed/refractory hairy cell leukemia (HCL; n = 28). The importance of minimal residual disease (MRD) after CR in HCL is unknown. A 21-patient extension cohort received 50 µg/kg every other day for 3 doses in 4-week cycles. These patients plus 12 previously reported at this upper dose level received 143 cycles without dose-limiting toxicity. The combined 33-patient cohort achieved 64% CR and 88% overall response rates, with median CR duration of 42.4 months. Of 32 50-µg/kg patients evaluable for MR...
Source: Blood - May 24, 2018 Category: Hematology Authors: Kreitman, R. J., Tallman, M. S., Robak, T., Coutre, S., Wilson, W. H., Stetler-Stevenson, M., FitzGerald, D. J., Santiago, L., Gao, G., Lanasa, M. C., Pastan, I. Tags: Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations Source Type: research

Novel insights into the pathogenesis of T-cell lymphomas
T-cell lymphomas are a heterogeneous group of rare malignancies with overlapping clinical, immunologic, and histologic features. Recent advances in our understanding of T-cell differentiation based on gene expression profiling, next-generation sequencing, and transgenic mouse modeling studies have better elucidated the pathogenetic mechanisms underlying the diverse biology of T-cell lymphomas. These studies show that although genetic alterations in epigenetic modifiers are implicated in all subtypes of T-cell lymphomas, specific subtypes demonstrate enrichment for particular recurrent alterations targeting specific genes. ...
Source: Blood - May 24, 2018 Category: Hematology Authors: Van Arnam, J. S., Lim, M. S., Elenitoba-Johnson, K. S. J. Tags: Lymphoid Neoplasia, Review Articles, Review Series Source Type: research

Genetics of diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL), the most frequent subtype of lymphoid malignancy, remains a significant clinical challenge, as ~30% of patients are not cured. Over the past decade, remarkable progress has been made in the understanding of the pathogenesis of this disease, spurred by the implementation of powerful genomic technologies that enabled the definition of its genetic and epigenetic landscape. These studies have uncovered a multitude of genomic alterations that contribute to the initiation and maintenance of the tumor clone by disrupting biological functions known to be critical for the normal biology of its...
Source: Blood - May 24, 2018 Category: Hematology Authors: Pasqualucci, L., Dalla-Favera, R. Tags: Lymphoid Neoplasia, Review Articles, Review Series Source Type: research

Critical influences on the pathogenesis of follicular lymphoma
The development of follicular lymphoma (FL) from a founder B cell with an upregulation of B-cell lymphoma 2 (BCL2), via the t(14;18) translocation, to a proliferating clone, poised to undergo further transformation to an aggressive lymphoma, illustrates the opportunistic Darwinian process of tumorigenesis. Protection against apoptosis allows an innocent cell to persist and divide, with dangerous accumulation of further mutational changes, commonly involving inactivation of chromatin-modifying genes. But this is not all. FL cells reflect normal B cells in relying on expression of surface immunoglobulin. In doing so, they ad...
Source: Blood - May 24, 2018 Category: Hematology Authors: Küppers, R., Stevenson, F. K. Tags: Lymphoid Neoplasia, Review Articles, Review Series Source Type: research

Chronic lymphocytic leukemia and mantle cell lymphoma: crossroads of genetic and microenvironment interactions
Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are 2 well-defined entities that diverge in their basic pathogenic mechanisms and clinical evolution but they share epidemiological characteristics, cells of origin, molecular alterations, and clinical features that differ from other lymphoid neoplasms. CLL and MCL are classically considered indolent and aggressive neoplasms, respectively. However, the clinical evolution of both tumors is very heterogeneous, with subsets of patients having stable disease for a long time whereas others require immediate intervention. Both CLL and MCL include 2 major molecular...
Source: Blood - May 24, 2018 Category: Hematology Authors: Puente, X. S., Jares, P., Campo, E. Tags: Lymphoid Neoplasia, Review Articles, Review Series Source Type: research

Five years of ibrutinib in CLL
(Source: Blood)
Source: Blood - May 24, 2018 Category: Hematology Authors: Forconi, F. Tags: Free Research Articles COMMENTS Source Type: research

The future of kinase inhibitors for DLBCL?
(Source: Blood)
Source: Blood - May 24, 2018 Category: Hematology Authors: Herman, S. E. M. Tags: Free Research Articles COMMENTS Source Type: research

MRD in HCL: does it matter?
(Source: Blood)
Source: Blood - May 24, 2018 Category: Hematology Authors: Ravandi, F. Tags: Free Research Articles COMMENTS Source Type: research

Introduction to a review series on biological insights into lymphoid tumors
(Source: Blood)
Source: Blood - May 24, 2018 Category: Hematology Authors: Stevenson, F. K. Tags: Free Research Articles, Lymphoid Neoplasia, Review Series EDITORIALS Source Type: research

A single-cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice
Hematopoietic stem and progenitor cells (HSPCs) maintain the adult blood system, and their dysregulation causes a multitude of diseases. However, the differentiation journeys toward specific hematopoietic lineages remain ill defined, and system-wide disease interpretation remains challenging. Here, we have profiled 44 802 mouse bone marrow HSPCs using single-cell RNA sequencing to provide a comprehensive transcriptional landscape with entry points to 8 different blood lineages (lymphoid, megakaryocyte, erythroid, neutrophil, monocyte, eosinophil, mast cell, and basophil progenitors). We identified a common basophil/mast ce...
Source: Blood - May 24, 2018 Category: Hematology Authors: Dahlin, J. S., Hamey, F. K., Pijuan-Sala, B., Shepherd, M., Lau, W. W. Y., Nestorowa, S., Weinreb, C., Wolock, S., Hannah, R., Diamanti, E., Kent, D. G., Göttgens, B., Wilson, N. K. Tags: Hematopoiesis and Stem Cells, e-Blood Source Type: research

A novel PDGFRB mutation in TKI-resistant Ph-like ALL
(Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Tags: Free Research Articles, CME article CONTINUING MEDICAL EDUCATION (CME) QUESTIONS Source Type: research

Kruse-Jarres R, Johnsen JM. How I treat type 2B von Willebrand disease. Blood. 2018;131(12):1292-1300.
(Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Tags: Free Research Articles ERRATUM Source Type: research

Pallasch CP, Schulz A, Kutsch N, et al. Overexpression of TOSO in CLL is triggered by B-cell receptor signaling and associated with progressive disease. Blood. 2008;112(10):4213-4219.
(Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Tags: Free Research Articles ERRATUM Source Type: research

25-Hydroxyvitamin D3-1{alpha}-hydroxylase- and multiple cytokine-producing diffuse large B-cell lymphoma
(Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Authors: Nakayama, S., Matsuda, M. Tags: Free Research Articles, BloodWork, Myeloid Neoplasia, Lymphoid Neoplasia BLOOD WORK Source Type: research

RUNX1 mutations in pediatric acute myeloid leukemia are associated with distinct genetic features and an inferior prognosis
(Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Authors: Yamato, G., Shiba, N., Yoshida, K., Hara, Y., Shiraishi, Y., Ohki, K., Okubo, J., Park, M.-j., Sotomatsu, M., Arakawa, H., Kiyokawa, N., Tomizawa, D., Adachi, S., Taga, T., Horibe, K., Miyano, S., Ogawa, S., Hayashi, Y. Tags: Pediatric Hematology, Myeloid Neoplasia Letter to Blood Source Type: research

Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract
(Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Authors: Sharma, A., Oishi, N., Boddicker, R. L., Hu, G., Benson, H. K., Ketterling, R. P., Greipp, P. T., Knutson, D. L., Kloft-Nelson, S. M., He, R., Eckloff, B. W., Jen, J., Nair, A. A., Davila, J. I., Dasari, S., Lazaridis, K. N., Bennani, N. N., Wu, T.-T., No Tags: Lymphoid Neoplasia Letter to Blood Source Type: research

PDGFRB mutation and tyrosine kinase inhibitor resistance in Ph-like acute lymphoblastic leukemia
In this study, we identified a novel PDGFRB fusion gene, namely AGGF1-PDGFRB, and functionally characterized its oncogenic potential in vitro. Further genomic profiling of longitudinally collected samples during treatment revealed the emergence of a mutation, PDGFRBC843G, which directly conferred resistance to all generations of ABL TKIs, including imatinib, dasatinib, nilotinib, and ponatinib. PDGFRB-mutant leukemia cells are highly sensitive to multitarget kinase inhibitor CHZ868, suggesting potential therapeutic options for some patients resistant to ABL TKIs. In summary, we describe a complex clonal evolution pattern i...
Source: Blood - May 17, 2018 Category: Hematology Authors: Zhang, Y., Gao, Y., Zhang, H., Zhang, J., He, F., Hnizda, A., Qian, M., Liu, X., Gocho, Y., Pui, C.-H., Cheng, T., Wang, Q., Yang, J. J., Zhu, X., Liu, X. Tags: Free Research Articles, Lymphoid Neoplasia, CME article, Brief Reports Source Type: research

SOX11 augments BCR signaling to drive MCL-like tumor development
We report here that overexpression of SOX11 in B cells promotes BCR signaling and a disease phenotype that mimics human MCL. (Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Authors: Kuo, P.-Y., Jatiani, S. S., Rahman, A. H., Edwards, D., Jiang, Z., Ahr, K., Perumal, D., Leshchenko, V. V., Brody, J., Shaknovich, R., Ye, B. H., Parekh, S. Tags: Lymphoid Neoplasia Source Type: research

The tumor suppressive TGF-{beta}/SMAD1/S1PR2 signaling axis is recurrently inactivated in diffuse large B-cell lymphoma
In this study, we examined the upstream regulators of S1PR2 expression and have newly identified the transforming growth factor-β (TGF-β)/TGF-βR2/SMAD1 axis as critically involved in S1PR2 transcriptional activation. Phosphorylated SMAD1 directly binds to regulatory elements in the S1PR2 locus as assessed by chromatin immunoprecipitation, and the CRISPR-mediated genomic editing of S1PR2, SMAD1, or TGFBR2 in DLBCL cell lines renders cells unresponsive to TGF-β–induced apoptosis. DLBCL clones lacking any 1 of the 3 factors have a clear growth advantage in vitro, as well as in subcutaneous xenotransp...
Source: Blood - May 17, 2018 Category: Hematology Authors: Stelling, A., Hashwah, H., Bertram, K., Manz, M. G., Tzankov, A., Müller, A. Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia Source Type: research

Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
Despite the well-established cell-intrinsic role of epigenetic factors in normal and malignant hematopoiesis, their cell-extrinsic role remains largely unexplored. Herein we investigated the hematopoietic impact of inactivating Ezh2, a key component of polycomb repressive complex 2 (PRC2), in the fetal liver (FL) vascular niche. Hematopoietic specific (Vav-iCre) Ezh2 inactivation enhanced FL hematopoietic stem cell (HSC) expansion with normal FL erythropoiesis. In contrast, endothelium (Tie2-Cre) targeted Ezh2 inactivation resulted in embryonic lethality with severe anemia at embryonic day 13.5 despite normal emergence of ...
Source: Blood - May 17, 2018 Category: Hematology Authors: Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J. Tags: Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis Source Type: research

How I treat the postthrombotic syndrome
This article uses a case-based approach to discuss risk factors for PTS after DVT, how to diagnose PTS, and available means to prevent and treat PTS, with a focus on new information in the field. (Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Authors: Rabinovich, A., Kahn, S. R. Tags: How I Treat, Free Research Articles, Thrombosis and Hemostasis Source Type: research

Tolerogenic properties of the Fc portion of IgG and its relevance to the treatment and management of hemophilia
Hemophilia, or inherited genetic deficiencies in coagulation factors, results in uncontrolled bleeding requiring replacement therapy with recombinant proteins given preventively or on demand. However, a major problem with these approaches is the potential for development of immune responses to the administered proteins due to the underlying genetic deficiency of the factor(s) throughout life. As such, there is great interest in developing strategies that avoid immunogenicity and induce immune tolerance. Recently, recombinant factor VIII (rFVIII) and rFIX fused to the crystallizable fragment (Fc) domain of immunoglobulin G ...
Source: Blood - May 17, 2018 Category: Hematology Authors: Blumberg, R. S., Lillicrap, D., the IgG Fc Immune Tolerance Group Tags: Immunobiology and Immunotherapy, Thrombosis and Hemostasis, Review Articles Source Type: research

Biomarkers for posttransplantation outcomes
This article provides an overview of the candidate biomarkers for clinical evaluation and outlines a path from biomarker discovery to first clinical correlation, to validation in independent cohorts, to a biomarker-based clinical trial, and finally to general clinical application. This article focuses on biomarkers discovered with a large-scale proteomics platform and validated with the same reproducible assay in at least 2 independent cohorts with sufficient sample size according to the 2014 National Institutes of Health consensus on biomarker criteria, as well as on biomarkers as tests for risk stratification of outcomes...
Source: Blood - May 17, 2018 Category: Hematology Authors: Paczesny, S. Tags: Perspectives, Immunobiology and Immunotherapy, Transplantation, Clinical Trials and Observations Source Type: research

Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study
An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity. Nearly all newborns were treated with phototherapy (93%), and many were treated with exchange transfu...
Source: Blood - May 17, 2018 Category: Hematology Authors: Grace, R. F., Bianchi, P., van Beers, E. J., Eber, S. W., Glader, B., Yaish, H. M., Despotovic, J. M., Rothman, J. A., Sharma, M., McNaull, M. M., Fermo, E., Lezon-Geyda, K., Morton, D. H., Neufeld, E. J., Chonat, S., Kollmar, N., Knoll, C. M., Kuo, K., K Tags: Plenary Papers, Red Cells, Iron, and Erythropoiesis, Clinical Trials and Observations Source Type: research

TKI resistance in Ph-like ALL
(Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Authors: Roberts, K. G. Tags: Free Research Articles COMMENTS Source Type: research

Ezh2 spares KitL from the cutter
(Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Authors: Pietras, E. M. Tags: Free Research Articles COMMENTS Source Type: research

Function and dysfunction
(Source: Blood)
Source: Blood - May 17, 2018 Category: Hematology Authors: Mohandas, N. Tags: Free Research Articles COMMENTS Source Type: research

Frequent erythrophagocytosis by leukemic blasts in B-cell acute lymphoblastic leukemia
(Source: Blood)
Source: Blood - May 10, 2018 Category: Hematology Authors: Olaiya, O. O., Li, W. Tags: Free Research Articles, BloodWork, Lymphoid Neoplasia BLOOD WORK Source Type: research

Pautrier-like microabscesses in the tonsil
(Source: Blood)
Source: Blood - May 10, 2018 Category: Hematology Authors: Matsuda, I., Hirota, S. Tags: Free Research Articles, BloodWork, Lymphoid Neoplasia BLOOD WORK Source Type: research

Long-term evaluation of physical improvement and survival of autologous stem cell transplantation in POEMS syndrome
(Source: Blood)
Source: Blood - May 10, 2018 Category: Hematology Authors: Ohwada, C., Sakaida, E., Kawajiri-Manako, C., Nagao, Y., Oshima-Hasegawa, N., Togasaki, E., Muto, T., Tsukamoto, S., Mitsukawa, S., Takeda, Y., Mimura, N., Takeuchi, M., Shimizu, N., Misawa, S., Iseki, T., Kuwabara, S., Nakaseko, C. Tags: Multiple Myeloma, Transplantation, Lymphoid Neoplasia Letter to Blood Source Type: research

Paraoxonase-2 regulates coagulation activation through endothelial tissue factor
Oxidative stress and inflammation of the vessel wall contribute to prothrombotic states. The antioxidative protein paraoxonase-2 (PON2) shows reduced expression in human atherosclerotic plaques and endothelial cells in particular. Supporting a direct role for PON2 in cardiovascular diseases, Pon2 deficiency in mice promotes atherogenesis through incompletely understood mechanisms. Here, we show that deregulated redox regulation in Pon2 deficiency causes vascular inflammation and abnormalities in blood coagulation. In unchallenged Pon2–/– mice, we find increased oxidative stress and endothelial dysfunction. Bone...
Source: Blood - May 10, 2018 Category: Hematology Authors: Ebert, J., Wilgenbus, P., Teiber, J. F., Jurk, K., Schwierczek, K., Döhrmann, M., Xia, N., Li, H., Spiecker, L., Ruf, W., Horke, S. Tags: Thrombosis and Hemostasis, Vascular Biology Source Type: research

Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism
It is uncertain whether antiphospholipid antibodies (APAs) increase the risk of recurrence after a first unprovoked venous thromboembolism (VTE). We tested for anticardiolipin antibodies, anti–β2 glycoprotein 1 antibodies, and lupus anticoagulant on 2 occasions ~6 months apart in 307 patients with a first unprovoked VTE who were part of a prospective cohort study. We then determined if APAs were associated with recurrent thrombosis in the 290 patients who stopped anticoagulant therapy in response to negative D-dimer results. Compared with those without an APA, the hazard ratios for recurrent VTE were 1.8 (95% co...
Source: Blood - May 10, 2018 Category: Hematology Authors: Kearon, C., Parpia, S., Spencer, F. A., Baglin, T., Stevens, S. M., Bauer, K. A., Lentz, S. R., Kessler, C. M., Douketis, J. D., Moll, S., Kaatz, S., Schulman, S., Connors, J. M., Ginsberg, J. S., Spadafora, L., Bhagirath, V., Liaw, P. C., Weitz, J. I., J Tags: Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research

Active enhancer and chromatin accessibility landscapes chart the regulatory network of primary multiple myeloma
Multiple myeloma (MM) is an aggressive cancer that originates from antibody-secreting plasma cells. Although genetically and transcriptionally well characterized, the aberrant gene regulatory networks that underpin this disease remain poorly understood. Here, we mapped regulatory elements, open chromatin, and transcription factor (TF) footprints in primary MM cells. In comparison with normal antibody-secreting cells, MM cells displayed consistent changes in enhancer activity that are connected to superenhancer (SE)-mediated deregulation of TF genes. MM cells also displayed widespread decompaction of heterochromatin that wa...
Source: Blood - May 10, 2018 Category: Hematology Authors: Jin, Y., Chen, K., De Paepe, A., Hellqvist, E., Krstic, A. D., Metang, L., Gustafsson, C., Davis, R. E., Levy, Y. M., Surapaneni, R., Wallblom, A., Nahi, H., Mansson, R., Lin, Y. C. Tags: Multiple Myeloma, Lymphoid Neoplasia Source Type: research

Mechanisms of resistance to EZH2 inhibitors in diffuse large B-cell lymphomas
In this study, we used this information for identifying the mechanisms of resistance to enhancer of zeste homolog 2 (EZH2) inhibitors in diffuse large B-cell lymphoma (DLBCL) harboring EZH2 mutations. We discovered that EZH2 inhibitor-resistant DLBCL cells showed activation of the insulin-like growth factor 1 receptor (IGF-1R), MEK, and phosphoinositide-3-kinase (PI3K) pathways. Constitutive activation of IGF-1R, MEK, or PI3K pathways was sufficient to confer resistance to EZH2 inhibitors in DLBCL. The activation of the PI3K/AKT and MAPK pathways decreased TNFSF10 and BAD expression through a FOXO3-dependent mechanism, whi...
Source: Blood - May 10, 2018 Category: Hematology Authors: Bisserier, M., Wajapeyee, N. Tags: Lymphoid Neoplasia Source Type: research

Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas
This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30+ peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (...
Source: Blood - May 10, 2018 Category: Hematology Authors: Fanale, M. A., Horwitz, S. M., Forero-Torres, A., Bartlett, N. L., Advani, R. H., Pro, B., Chen, R. W., Davies, A., Illidge, T., Uttarwar, M., Lee, S.-Y., Ren, H., Kennedy, D. A., Shustov, A. R. Tags: Lymphoid Neoplasia, Brief Reports, Clinical Trials and Observations Source Type: research

The identification of fibrosis-driving myofibroblast precursors reveals new therapeutic avenues in myelofibrosis
Myofibroblasts are fibrosis-driving cells and are well characterized in solid organ fibrosis, but their role and cellular origin in bone marrow fibrosis remains obscure. Recent work has demonstrated that Gli1+ and LepR+ mesenchymal stromal cells (MSCs) are progenitors of fibrosis-causing myofibroblasts in the bone marrow. Genetic ablation of Gli1+ MSCs or pharmacologic targeting of hedgehog (Hh)-Gli signaling ameliorated fibrosis in mouse models of myelofibrosis (MF). Moreover, pharmacologic or genetic intervention in platelet-derived growth factor receptor α (Pdgfrα) signaling in Lepr+ stromal cells suppressed...
Source: Blood - May 10, 2018 Category: Hematology Authors: Kramann, R., Schneider, R. K. Tags: Perspectives, Hematopoiesis and Stem Cells, Myeloid Neoplasia Source Type: research

Antiphospholipid antibodies induce thrombosis by PP2A activation via apoER2-Dab2-SHC1 complex formation in endothelium
In the antiphospholipid syndrome (APS), antiphospholipid antibody (aPL) recognition of β2 glycoprotein I promotes thrombosis, and preclinical studies indicate that this is due to endothelial nitric oxide synthase (eNOS) antagonism via apolipoprotein E receptor 2 (apoER2)-dependent processes. How apoER2 molecularly links these events is unknown. Here, we show that, in endothelial cells, the apoER2 cytoplasmic tail serves as a scaffold for aPL-induced assembly and activation of the heterotrimeric protein phosphatase 2A (PP2A). Disabled-2 (Dab2) recruitment to the apoER2 NPXY motif promotes the activating L309 methylatio...
Source: Blood - May 10, 2018 Category: Hematology Authors: Sacharidou, A., Chambliss, K. L., Ulrich, V., Salmon, J. E., Shen, Y.-M., Herz, J., Hui, D. Y., Terada, L. S., Shaul, P. W., Mineo, C. Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology Source Type: research

Tissue factor and oxidative stress
(Source: Blood)
Source: Blood - May 10, 2018 Category: Hematology Authors: Mackman, N., Antoniak, S. Tags: Free Research Articles COMMENTS Source Type: research

"Antiphospholipids": the more, the worse?
(Source: Blood)
Source: Blood - May 10, 2018 Category: Hematology Authors: Wahl, D. Tags: Free Research Articles COMMENTS Source Type: research

The antiphospholipid syndrome finally fathomed?
(Source: Blood)
Source: Blood - May 10, 2018 Category: Hematology Authors: de Groot, P. G. Tags: Free Research Articles COMMENTS Source Type: research

Diffuse large B-cell lymphoma with strong aberrant expression of CD31
(Source: Blood)
Source: Blood - May 3, 2018 Category: Hematology Authors: Hu, S., Wang, Y. Tags: Free Research Articles, BloodWork, Lymphoid Neoplasia BLOOD WORK Source Type: research