46,137 results match your criteria Blood[Journal]


Warfarin, a juggler's demise.

Blood 2018 Jun;131(25):2742-2743

The Scripps Research Institute.

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Shielding p53 from destruction.

Authors:
Deepa Sampath

Blood 2018 Jun;131(25):2740-2741

The Ohio State University.

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Drawing the line of ineligibility.

Authors:
Anita J Kumar

Blood 2018 Jun;131(25):2739-2740

Tufts Medical Center.

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Impact of spliceosome mutations on RNA splicing in myelodysplasia: dysregulated genes/pathways and clinical associations.

Blood 2018 Jun 21. Epub 2018 Jun 21.

Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford and Haematology Theme Oxford Biomedical Research Centre, Oxford, United Kingdom;

SF3B1, SRSF2 and U2AF1 are the most frequently mutated splicing factor genes in the myelodysplastic syndromes (MDS). We have performed a comprehensive and systematic analysis to determine the impact of these commonly mutated splicing factors on pre-mRNA splicing in the bone marrow stem/progenitor cells and in the erythroid and myeloid precursors in splicing factor mutant MDS. Using RNA-seq, we determined the aberrantly spliced genes and dysregulated pathways in CD34 cells of 84 MDS patients. Read More

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Non-viral RNA chimeric antigen receptor modified T cells in patients with Hodgkin lymphoma.

Blood 2018 Jun 20. Epub 2018 Jun 20.

Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States.

Chimeric antigen receptor (CAR) modified T cells are being investigated in many settings including classical Hodgkin lymphoma (cHL). The unique biology of cHL, characterized by scant Hodgkin and Reed-Sternberg (HRS) cells within an immunosuppressive tumor microenvironment (TME), may pose challenges for cellular therapies directly targeting antigens expressed on HRS. We hypothesized that eradicating CD19 positive (+) B cells within the TME and the putative circulating CD19+ HRS clonotypic cells using anti-CD19 directed CAR modified T cells (CART19) may indirectly affect HRS cells, which do not express CD19. Read More

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Peptidoglycan induces disseminated intravascular coagulation in baboons through activation of both coagulation pathways.

Blood 2018 Jun 19. Epub 2018 Jun 19.

Department of Arthritis and Clinical immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States;

Anthrax infections exhibit progressive coagulopathies that may contribute to the sepsis pathophysiology observed in fulminant disease. The hemostatic imbalance is recapitulated in primate models of late-stage disease but is uncommon in toxemic models suggesting contribution of other bacterial pathogen associated molecular patterns (PAMPs). Peptidoglycan (PGN) is a bacterial PAMP that engages cellular components at the crosstalk between innate immunity and hemostasis. Read More

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Dynamic intercellular redistribution of HIT antigen modulates heparin-induced thrombocytopenia.

Blood 2018 Jun 18. Epub 2018 Jun 18.

Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies to platelet factor 4 (PF4)/heparin complexes. PF4 released from platelets binds to surface glycosaminoglycans on hematopoietic and vascular cells that are heterogenous in composition and differ in affinity for PF4. PF4 binds to monocytes with higher affinity than to platelets, and depletion of monocytes exacerbates thrombocytopenia in a murine HIT model. Read More

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Mutations in gene cause severe congenital neutropenia as well as Shwachman-Diamond-like syndrome.

Blood 2018 Jun 18. Epub 2018 Jun 18.

Department of Pediatric Hematology and Oncology, Trousseau Hospital, AP-HP, Paris, France.

Congenital neutropenias (CN) are rare heterogeneous genetic disorders with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation in the gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and one autosomal dominant family. We subsequently sequenced the gene in 66 probands from the French CN registry. Read More

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Translating anti-CD19 CAR T-Cell therapy into clinical practice for relapsed/refractory diffuse large B-Cell lymphoma.

Blood 2018 Jun 18. Epub 2018 Jun 18.

Department of Medicine, Division of Medical Oncology, Clinical Research Division, University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, United States

Chimeric antigen receptor (CAR) T-cells demonstrate efficacy in B-cell malignancies, leading to FDA approval of axicaptagene ciloleucel in October 2017 and tisagenlecleucel in May 2018 for large B-cell lymphomas after two prior lines of therapy. Durable remissions are seen in 30-40% of study-treated patients, but unique toxicities of cytokine release syndrome and neurotoxicity require administration in specialized centers. This article reviews the data to-date within the context of current diffuse large B-cell lymphoma management, focusing on axicaptagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel. Read More

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Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy.

Blood 2018 Jun 14. Epub 2018 Jun 14.

Institute of Pharmacology and Toxicology, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, Austria.

Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 MPN patients including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. Read More

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initiates myeloid bias and myelodysplastic/myeloproliferative syndrome (MDS/MPN) from hemopoietic stem cells.

Blood 2018 Jun 14. Epub 2018 Jun 14.

St. Vincent's Institute, Fitzroy, VIC, Australia;

Mutations in occur in myelodysplastic (MDS) and myelodysplastic/myeloproliferative (MDS/MPN) syndromes. mutations cluster at proline 95, with the most frequent a histidine (P95H) substitution. They undergo positive selection, arise early in the course of disease and have been identified in age-related clonal hemopoiesis. Read More

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Heparin-induced thrombocytopenia and thrombosis during high dose melphalan and autologous stem cell transplantation.

Blood 2018 Jun 14. Epub 2018 Jun 14.

Stem cell transplantation program of the Section of Hematology and Medical Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA, United States.

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Surviving childhood cancer: a sobering story.

Authors:
Mary Eapen

Blood 2018 Jun;131(24):2603-2604

Medical College of Wisconsin.

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HBV messing with the B-cell genome leads to DLBCL.

Blood 2018 Jun;131(24):2602-2603

Sapienza University of Rome Medical School.

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Btk inhibitors in atherosclerosis.

Blood 2018 Jun;131(24):2601-2602

Oregon Health and Science University.

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Congenital macrothrombocytopenia with focal myelofibrosis due to mutations in human G6b-B is rescued in humanized mice.

Blood 2018 Jun 13. Epub 2018 Jun 13.

Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

Unlike primary myelofibrosis (PMF) in adults, myelofibrosis in children is rare. Congenital (inherited) forms of myelofibrosis (cMF) have been described, but the underlying genetic mechanisms remain elusive. Here we describe 4 families with autosomal recessive inherited macrothrombocytopenia with focal myelofibrosis due to germline loss-of-function mutations in the megakaryocyte-specific immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptor G6b-B (G6b, C6orf25 or MPIG6B). Read More

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Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells associate with clinical outcomes in NHL.

Blood 2018 Jun 12. Epub 2018 Jun 12.

Kite, a Gilead Company, Santa Monica, CA, United States

After treatment with chimeric antigen receptor (CAR) T cells, interleukin (IL)-15 elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines including interferon-γ (IFN-γ), IL-17A, IL-8, and macrophage inflammatory protein 1-α. Read More

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June 2018
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Treatment strategies for adolescent and young adult patients with acute myeloid leukemia.

Blood 2018 Jun 12. Epub 2018 Jun 12.

Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA, United States

Adolescents and young adults (AYA) form a unique group of patients with newly diagnosed acute myeloid leukemia. They differ in terms of disease biology, psychosocial challenges, survival and in other important respects from children as well as from middle age and older adults. AYA may be treated using pediatric protocols, developed in trials comprised primarily of younger patients, or using adult protocols, developed in trials comprised primarily of older patients. Read More

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Management of aggressive B cell NHLs in the AYA population: an adult versus pediatric perspective.

Blood 2018 Jun 12. Epub 2018 Jun 12.

Center for Global Health, National Cancer Institute, Bethesda, MD, United States.

The adolescents and young adult (AYA) population represent a group where mature B-cell lymphomas constitute a significant proportion of the overall malignancies that occur. Among these are aggressive B-cell non-Hodgkin lymphomas (NHLs) which are predominantly diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL). For the most part, there is remarkable divide in how pediatric/adolescent patients (under the age of 18 years) with lymphoma are treated versus their young adult counterparts and molecular data are lacking, especially in pediatric and AYA series. Read More

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The management of Hodgkin lymphoma in adolescents and young adults: burden of disease or burden of choice?

Blood 2018 Jun 12. Epub 2018 Jun 12.

Department of Global Pediatric Medicine, St. Jude Children's Research Hospital and the University of Tennessee Health Sciences Center, Memphis, TN, United States.

Adolescents and young adults (AYAs) comprise the largest age group affected by Hodgkin lymphoma (HL). Despite excellent overall survival of AYA patients with HL due to advances in treatment regimens, therapy-associated late effects continue to be a concern in HL survivors, especially for younger patients who have decades of life remaining. Since the first clinical trial for HL with chemotherapy in 1964, subsequent protocols have attempted to reduce chemotherapy-induced toxicities and yet maintain high overall survival rates. Read More

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Psychosocial challenges and health-related quality of life of adolescents and young adults with hematologic malignancies.

Blood 2018 Jun 12. Epub 2018 Jun 12.

Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, Netherlands.

Adolescents and young adults (AYA) occupy a unique place within the hematologic malignancy community due to the challenges they face related to their disease biology, physical, psychosocial and economic circumstances, and issues related to access to care and long-term follow-up. Efforts to define age-specific (supportive) care needs and targets for intervention in these areas are evolving. This review discusses the psychosocial issues AYA with hematologic malignancies are dealing with, how these might affect their health-related quality of life (HRQoL), and the challenges in delivering high quality supportive care to this underserved population. Read More

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Introduction to a review series on Adolescent and Young Adult Malignant Hematology.

Authors:
Jorge Cortes

Blood 2018 Jun 12. Epub 2018 Jun 12.

Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States

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Acute lymphoblastic leukemia in adolescent and young adults: treat as adults or as children?

Blood 2018 Jun 12. Epub 2018 Jun 12.

Pediatric Hematology and Immunology Department, Robert Debre Hospital Paris, France

Adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) are recognized as a unique population with specific characteristics and needs. In adolescents aged 15-20 years old, the use of full pediatric protocols is supported by many comparative studies of pediatric and adult cooperative groups. In young adults, growing evidence suggests that pediatric-inspired or even fully pediatric approaches may also dramatically improve outcomes, leading to long-term survival rates of almost 70%, despite diminishing indications of hematopoietic stem cell transplantation. Read More

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L-glutamine for sickle cell anemia: more questions than answers.

Authors:
Charles T Quinn

Blood 2018 Jun 12. Epub 2018 Jun 12.

Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

In 2017, the Food and Drug Administration (FDA) approved two medications for sickle cell anemia (SCA): hydroxyurea for children (≥2 years of age) and L-glutamine for children and adults (≥5 years). The approval of hydroxyurea for children was long overdue, having been authorized by the FDA for adults in 1998 and by the European Medicines Agency for adults and children in 2007, but the approval of L-glutamine was a surprise to many in the field. There are few published studies of L-glutamine as a treatment for SCA, so all can be reviewed in this brief manuscript. Read More

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Uncoupling of the ITIM receptor G6b-B from the tyrosine phosphatases Shp1 and Shp2 disrupts platelet homeostasis in mice.

Blood 2018 Jun 11. Epub 2018 Jun 11.

Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom;

The immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptor G6b-B has emerged as a key regulator of platelet homeostasis. However, it remains unclear how it mediates its effects. Tyrosine phosphorylation of the ITIM and immunoreceptor tyrosine-based switch motif (ITSM) within the cytoplasmic tail of G6b-B provides a docking site for SH2 domain-containing protein-tyrosine phosphatases Shp1 and Shp2, which are also critical regulators of platelet production and function. Read More

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Aged murine hematopoietic stem cells drive aging-associated immune remodeling.

Blood 2018 Jun 11. Epub 2018 Jun 11.

Department of Internal Medicine I, University Hospital of Ulm, Ulm, Germany.

Aging-associated remodeling of the immune system impairs its functional integrity and contributes to increased morbidity and mortality in the elderly. Aging of hematopoietic stem cells (HSCs), from which all cells of the adaptive immune system ultimately originate, might play a crucial role in the remodeling of the aged immune system. We recently reported that aging of HSCs is, in part, driven by elevated activity of the small RhoGTPase Cdc42 and that aged HSCs can be rejuvenated in vitro by inhibition of the elevated Cdc42 activity in aged HSCs with the pharmacological compound CASIN. Read More

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June 2018
1 Read

New lessons from an old gene: complex splicing and a novel cryptic exon in VHL gene cause erythrocytosis and VHL disease.

Blood 2018 Jun 11. Epub 2018 Jun 11.

Laboratory of Excellence GR-Ex, Ecole Pratique des Hautes, EPHE, PSL research University, CRCINA, INSERM, Universite de Nantes, Nantes, France

Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. Since this discovery, additional VHL mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. Read More

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June 2018
2 Reads

Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma.

Blood 2018 Jun 8. Epub 2018 Jun 8.

Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

Understanding the profile of oncogene and tumor suppressor gene mutations with their interactions and impact on the prognosis of multiple myeloma (MM) can improve the definition of disease subsets and identify pathways important in disease pathobiology. Using integrated genomics of 1,273 newly diagnosed patients with multiple myeloma we identify 63 driver genes, some of which are novel including , , , , and Oncogene mutations are significantly more clonal than tumor suppressor mutations, indicating they may exert a bigger selective pressure. Patients with more mutations in driver genes are associated with a worse outcome, as are those with identified mechanisms of genomic instability. Read More

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Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells.

Blood 2018 Jun 8. Epub 2018 Jun 8.

Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, TX, United States;

Induction of red blood cell fetal hemoglobin (HbF, α2γ2) ameliorates the pathophysiology of sickle cell disease (SCD) by reducing the concentration of sickle hemoglobin (HbS, α2β2) to inhibit its polymerization. Hydroxyurea (HU), the only FDA-approved drug for SCD, acts in part by inducing HbF, but is not fully effective, reflecting the need for new therapies. Whole exome sequence analysis of rare genetic variants in SCD patients identified FOXO3 as a candidate regulator of RBC HbF. Read More

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Platelet satellitism around cytoplasmic fragments of neoplastic lymphocytes.

Blood 2018 Jun;131(23):2599

Zhongshan Hospital Fudan University.

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June 2018
1 Read

Stress erythropoiesis: selenium to the rescue!

Blood 2018 Jun;131(23):2512-2513

The Feinstein Institute for Medical Research; Donald & Barbara Zucker School of Medicine at Hofstra/Northwell.

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Can IL-15 superagonist ALTer GVL?

Authors:
Robert J Soiffer

Blood 2018 Jun;131(23):2511-2512

Dana-Farber Cancer Institute.

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Mass cytometry of Hodgkin lymphoma reveals a CD4 exhausted T-effector and T-regulatory cell rich microenvironment.

Blood 2018 Jun 7. Epub 2018 Jun 7.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States;

In classical Hodgkin lymphoma (cHL), the host anti-tumor immune response is ineffective. Hodgkin Reed-Sternberg (HRS) cells have multifaceted mechanisms to evade the immune system including 9p24.1// genetic alterations, overexpression of the PD-1 ligands and associated T-cell exhaustion and additional structural bases of aberrant antigen presentation. Read More

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June 2018
3 Reads

Extracellular galectins as controllers of cytokines in hematological cancer.

Blood 2018 Jun 6. Epub 2018 Jun 6.

de Duve Institute, Universite catholique de Louvain, Brussels, Belgium

Galectins and cytokines are both secreted proteins whose levels are prognosis factors for several cancers. Extracellular galectins bind to the glycans decorating glycoproteins and are overproduced in most cancers. Accumulative evidence shows that galectins regulate cytokines during cancer progression. Read More

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Phase 2b study of two dosing regimens of quizartinib monotherapy in FLT3-ITD mutated, relapsed or refractory AML.

Blood 2018 Jun 6. Epub 2018 Jun 6.

Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States.

This randomized, open-label, phase 2b study (NCT01565668) evaluated efficacy and safety of two dosing regimens of quizartinib monotherapy in patients with relapsed/refractory (R/R) FLT3-internal tandem duplication (ITD)-mutated acute myeloid leukemia (AML) who previously underwent transplant or one second-line salvage therapy. Patients (N=76) were randomized to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency ≥10% was defined as FLT3-ITD mutated disease. Read More

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HSP110 sustains chronic NF-κB signaling in activated B cell diffuse large B cell lymphoma through MyD88 stabilization.

Blood 2018 Jun 5. Epub 2018 Jun 5.

Universite Bourgogne Franche-Comte, France;

Activated B cell diffuse large B cell lymphoma (ABC-DLBCL) is an aggressive lymphoproliferative disorder involving chronic NF-κB activation. Several mutations in the BCR and the MyD88 signaling pathway components, such as MyD88 L265P, are implicated in this aberrant activation. Among heat-shock proteins, HSP110 has recently been identified as a pro- survival and/or proliferation factor in many cancers but its role in ABC-DLBCL survival mechanisms remained to be established. Read More

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June 2018
2 Reads

Exploring traditional and non-traditional roles for thrombomodulin.

Blood 2018 Jun 4. Epub 2018 Jun 4.

Centre for Blood Research, Division of Hematology-Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada

Thrombomodulin (TM) is an integral component of a multi-molecular system, localized primarily to the vascular endothelium, that integrates crucial biological processes and biochemical pathways, including those related to coagulation, innate immunity, inflammation and cell proliferation. These are designed to protect the host from injury and to promote healing. The "traditional role" of TM in hemostasis was determined with its discovery in the 1980s as a ligand for thrombin and a critical cofactor for the major natural anticoagulant protein C (PC) system, and subsequently for thrombin-mediated activation of the thrombin activatable fibrinolysis inhibitor (TAFI), (aka procarboxypeptidase B2 (proCBP2)). Read More

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