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Blood Advances

Céline Moison, Vincent-Philippe Lavallée, Clarisse Thiollier, Bernhard Lehnertz, Isabel Boivin, Nadine Mayotte, Yves Gareau, Mélanie Fréchette, Valérie Blouin-Chagnon, Sophie Corneau, Sylvie Lavallée, Sébastien Lemieux, Anne Marinier, Josée Hébert, Guy Sauvageau
Patients diagnosed with acute myeloid leukemia with complex karyotype (CK AML) have an adverse prognosis using current therapies, especially when accompanied by TP53 alterations. We hereby report the RNA-sequencing analysis of the 68 CK AML samples included in the Leucegene 415 patient cohort. We confirm the frequent occurrence of TP53 alterations in this subgroup and further characterize the allele expression profile and transcript alterations of this gene. We also document that the RAS pathway ( N / KRAS , NF1 , PTPN11 , BRAF ) is frequently altered in this disease...
February 26, 2019: Blood Advances
Muhammad Baghdadi, Kozo Ishikawa, Sayaka Nakanishi, Tomoki Murata, Yui Umeyama, Takuto Kobayashi, Yosuke Kameda, Hiraku Endo, Haruka Wada, Bjarne Bogen, Satoshi Yamamoto, Keisuke Yamaguchi, Ikumi Kasahara, Hiroshi Iwasaki, Mutsumi Takahata, Makoto Ibata, Shuichiro Takahashi, Hideki Goto, Takanori Teshima, Ken-Ichiro Seino
Multiple myeloma (MM) is a hematological malignancy that grows in multiple sites of the axial skeleton and causes debilitating osteolytic disease. Interleukin-34 (IL-34) is a newly discovered cytokine that acts as a ligand of colony-stimulating factor-1 (CSF-1) receptor and can replace CSF-1 for osteoclast differentiation. In this study, we identify IL-34 as an osteoclastogenic cytokine that accelerates osteolytic disease in MM. IL-34 was found to be expressed in the murine MM cell line MOPC315.BM, and the expression of IL-34 was enhanced by stimulation with proinflammatory cytokines or by bone marrow (BM) stromal cells...
February 26, 2019: Blood Advances
Ronald McCord, Christopher R Bolen, Hartmut Koeppen, Edward E Kadel, Mikkel Z Oestergaard, Tina Nielsen, Laurie H Sehn, Jeffrey M Venstrom
Programmed death-ligand 1 (PD-L1) and its receptor, programmed cell death-1 (PD-1), are important negative regulators of immune cell activation. Therapeutically targeting PD-1/PD-L1 in diffuse large B-cell lymphoma (DLBCL) patients with a single agent has limited activity, meriting a deeper understanding of this complex biology and of available PD-L1 clinical assays. In this study, we leveraged 2 large de novo DLBCL phase 3 trials (GOYA and MAIN) to better understand the biologic and clinical relevance of PD-L1 in de novo DLBCL...
February 26, 2019: Blood Advances
Duncan Murray, Jack Luke McMurray, Suzy Eldershaw, Hayden Pearce, Nathaniel Davies, Julia J Scarisbrick, Paul Moss
Immunotherapy is a valuable treatment for many cancer patients, and there is considerable interest in understanding the mechanisms of immune evasion to guide appropriate management. Mycosis fungoides (MF) is a malignant disorder of skin-homing CD4+ T cells, and it exhibits a highly variable clinical course during which the tumor-specific immune response may be an important determinant. An unusual feature of MF is that tumor-infiltrating lymphocytes (TILs) must attempt to control a malignant cell from within their own lineage...
February 26, 2019: Blood Advances
Guillermo Garcia-Manero, Yasmin Abaza, Koichi Takahashi, Bruno C Medeiros, Martha Arellano, Samer K Khaled, Mrinal Patnaik, Olatoyosi Odenike, Hamid Sayar, Mohan Tummala, Prapti Patel, Lori Maness-Harris, Robert Stuart, Elie Traer, Kasra Karamlou, Abdulraheem Yacoub, Richard Ghalie, Ruben Giorgino, Ehab Atallah
Pracinostat, a potent oral pan-histone deacetylase inhibitor with modest single-agent activity in acute myeloid leukemia (AML), has shown synergistic antitumor activity when combined with azacitidine. This single-group, multicenter phase 2 study assessed the safety and efficacy of pracinostat combined with azacitidine in patients who were at least 65 years old with newly diagnosed AML and who were ineligible for standard induction chemotherapy. Patients received pracinostat 60 mg/d, 3 d/wk, for 3 consecutive weeks, plus azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle...
February 26, 2019: Blood Advances
Hojun Li, Leslie A Benson, Lauren A Henderson, Isaac H Solomon, Alyssa L Kennedy, Ariane Soldatos, Bibiana Bielekova, Jennifer Murphy, Kimberly J Davies, Leslie E Lehmann, Michelle A Lee, Sanda Alexandrescu, Barbara A Degar, Mark P Gorman, Christine N Duncan
No abstract text is available yet for this article.
February 26, 2019: Blood Advances
Narendranath Epperla, Arwa Y Shana'ah, Dan Jones, Beth A Christian, Sabarish Ayyappan, Kami Maddocks, Jennifer A Woyach
No abstract text is available yet for this article.
February 26, 2019: Blood Advances
Tobias Tritschler, Philip S Wells
No abstract text is available yet for this article.
February 12, 2019: Blood Advances
Michelle M Castillo, Qiuhui Yang, Min Zhan, Amy Y Pan, Michael W Lawlor, Alan E Mast, Rashmi Sood
Tissue factor pathway inhibitor (TFPI) is a serine protease with multiple anticoagulant activities. The Kunitz1 (K1) domain of TFPI binds the active site of factor VIIa and is required for inhibition of tissue factor (TF)/factor VIIa catalytic activity. Mice lacking TFPI K1 domain die in utero. TFPI is highly expressed on trophoblast cells of the placenta. We used genetic strategies to selectively ablate exon 4 encoding TFPI K1 domain in the embryo, while maintaining expression in trophoblast cells. This approach resulted in expected Mendelian frequency of TFPI K1 domain-deficient mice...
February 12, 2019: Blood Advances
Asumi Yokota, Hideyo Hirai, Ryuichi Sato, Hiroko Adachi, Fumiko Sato, Yoshihiro Hayashi, Atsushi Sato, Naoka Kamio, Yasuo Miura, Masakazu Nakano, Daniel G Tenen, Shinya Kimura, Kei Tashiro, Taira Maekawa
Even in the era of ABL tyrosine kinase inhibitors, eradication of chronic myeloid leukemia (CML) stem cells is necessary for complete cure of the disease. Interferon-α (IFN-α) has long been used for the treatment of chronic-phase CML, but its mechanisms of action against CML stem cells remain unclear. We found that IFN-α upregulated CCAAT/enhancer binding protein β (C/EBPβ) in BCR-ABL-expressing mouse cells by activating STAT1 and STAT5, which were recruited to a newly identified 3' distal enhancer of Cebpb that contains tandemly aligned IFN-γ-activated site elements...
February 12, 2019: Blood Advances
Ornellie Bernadin, Fouzia Amirache, Anais Girard-Gagnepain, Ranjita Devi Moirangthem, Camille Lévy, Kuiying Ma, Caroline Costa, Didier Nègre, Christian Reimann, David Fenard, Agata Cieslak, Vahid Asnafi, Hanem Sadek, Rana Mhaidly, Marina Cavazzana, Chantal Lagresle-Peyrou, François-Loïc Cosset, Isabelle André, Els Verhoeyen
T cells represent a valuable tool for treating cancers and infectious and inherited diseases; however, they are mainly short-lived in vivo. T-cell therapies would strongly benefit from gene transfer into long-lived persisting naive T cells or T-cell progenitors. Here we demonstrate that baboon envelope glycoprotein pseudotyped lentiviral vectors (BaEV-LVs) far outperformed other LV pseudotypes for transduction of naive adult and fetal interleukin-7-stimulated T cells. Remarkably, BaEV-LVs efficiently transduced thymocytes and T-cell progenitors generated by culture of CD34+ cells on Delta-like ligand 4 (Dll4)...
February 12, 2019: Blood Advances
Emily M McWilliams, Christopher R Lucas, Timothy Chen, Bonnie K Harrington, Ronni Wasmuth, Amanda Campbell, Kerry A Rogers, Carolyn M Cheney, Xiaokui Mo, Leslie A Andritsos, Farrukh T Awan, Jennifer Woyach, William E Carson, Jonathan Butchar, Susheela Tridandapani, Erin Hertlein, Carlos E Castro, Natarajan Muthusamy, John C Byrd
The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib has transformed chronic lymphocytic leukemia (CLL) therapy but requires continuous administration. These factors have spurred interest in combination treatments. Unlike with chemotherapy, CD20-directed antibody therapy has not improved the outcome of BTKi treatment. Whereas CD20 antigen density on CLL cells decreases during ibrutinib treatment, the B-cell activating factor (BAFF) and its receptor (BAFF-R) remain elevated. Furthermore, BAFF signaling via noncanonical NF-κB remains elevated with BTKi treatment...
February 12, 2019: Blood Advances
(no author information available yet)
No abstract text is available yet for this article.
February 12, 2019: Blood Advances
William Bain, Tolani Olonisakin, Minting Yu, Yanyan Qu, Mei Hulver, Zeyu Xiong, Huihua Li, Joseph Pilewski, Rama K Mallampalli, Mehdi Nouraie, Anuradha Ray, Prabir Ray, Zhenyu Cheng, Robert M Q Shanks, Claudette St Croix, Roy L Silverstein, Janet S Lee
Thrombocytopenia is associated with worse outcomes in patients with acute respiratory distress syndrome, which is most commonly caused by infection and marked by alveolar-capillary barrier disruption. However, the mechanisms by which platelets protect the lung alveolar-capillary barrier during infectious injury remain unclear. We found that natively thrombocytopenic Mpl -/- mice deficient in the thrombopoietin receptor sustain severe lung injury marked by alveolar barrier disruption and hemorrhagic pneumonia with early mortality following acute intrapulmonary Pseudomonas aeruginosa (PA) infection; barrier disruption was attenuated by platelet reconstitution...
February 12, 2019: Blood Advances
Fang Dong, Haitao Bai, Xiaofang Wang, Shanshan Zhang, Zhao Wang, Miner Xie, Sen Zhang, Jinhong Wang, Sha Hao, Tao Cheng, Hideo Ema
The cell of origin, defined as the normal cell in which the transformation event first occurs, is poorly identified in leukemia, despite its importance in understanding of leukemogenesis and improving leukemia therapy. Although hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were used for leukemia models, whether their self-renewal and differentiation potentials influence the initiation and development of leukemia is largely unknown. In this study, the self-renewal and differentiation potentials in 2 distinct types of HSCs (HSC1 [CD150+ CD41- CD34- Lineage- Sca-1+ c-Kit+ cells] and HSC2 [CD150- CD41- CD34- Lineage- Sca-1+ c-Kit+ cells]) and 3 distinct types of HPCs (HPC1 [CD150+ CD41+ CD34- Lineage- Sca-1+ c-Kit+ cells], HPC2 [CD150+ CD41+ CD34+ Lineage- Sca-1+ c-Kit+ cells], and HPC3 [CD150- CD41- CD34+ Lineage- Sca-1+ c-Kit+ cells]) were isolated from adult mouse bone marrow, and examined by competitive repopulation assay...
February 12, 2019: Blood Advances
Kavita Bisht, Marion E Brunck, Taichi Matsumoto, Crystal McGirr, Bianca Nowlan, Whitney Fleming, Thomas Keech, Graham Magor, Andrew C Perkins, Julie Davies, Gail Walkinshaw, Lee Flippin, Ingrid G Winkler, Jean-Pierre Levesque
In normoxia, hypoxia-inducible transcription factors (HIFs) are rapidly degraded within the cytoplasm as a consequence of their prolyl hydroxylation by oxygen-dependent prolyl hydroxylase domain (PHD) enzymes. We have previously shown that hematopoietic stem and progenitor cells (HSPCs) require HIF-1 for effective mobilization in response to granulocyte colony-stimulating factor (G-CSF) and CXCR4 antagonist AMD3100/plerixafor. Conversely, HIF PHD inhibitors that stabilize HIF-1 protein in vivo enhance HSPC mobilization in response to G-CSF or AMD3100 in a cell-intrinsic manner...
February 12, 2019: Blood Advances
Koichi Miyamura, Takuya Yamashita, Yoshiko Atsuta, Tatsuo Ichinohe, Koji Kato, Naoyuki Uchida, Takahiro Fukuda, Kazuteru Ohashi, Hiroyasu Ogawa, Tetsuya Eto, Masami Inoue, Satoshi Takahashi, Takehiko Mori, Heiwa Kanamori, Hiromasa Yabe, Asahito Hama, Shinichiro Okamoto, Yoshihiro Inamoto
The need for long-term follow-up (LTFU) after allogeneic hematopoietic cell transplantation (HCT) has been increasingly recognized for managing late effects such as subsequent cancers and cardiovascular events. A substantial population, however, has already terminated LTFU at HCT centers. To better characterize follow-up termination, we analyzed the Japanese transplant registry database. The study cohort included 17 980 survivors beyond 2 years who underwent their first allogeneic HCT between 1974 and 2013...
February 12, 2019: Blood Advances
Alberto J Arribas, Andrea Rinaldi, Giorgia Chiodin, Ivo Kwee, Afua Adjeiwaa Mensah, Luciano Cascione, Davide Rossi, Meena Kanduri, Richard Rosenquist, Emanuele Zucca, Peter W Johnson, Gianluca Gaidano, Christopher C Oakes, Francesco Bertoni, Francesco Forconi
Classic hairy cell leukemia (HCL) is a tumor of mature clonal B cells with unique genetic, morphologic, and phenotypic features. DNA methylation profiling has provided a new tier of investigation to gain insight into the origin and behavior of B-cell malignancies; however, the methylation profile of HCL has not been specifically investigated. DNA methylation profiling was analyzed with the Infinium HumanMethylation27 array in 41 mature B-cell tumors, including 11 HCL, 7 splenic marginal zone lymphomas (SMZLs), and chronic lymphocytic leukemia with an unmutated (n = 7) or mutated (n = 6) immunoglobulin gene heavy chain variable (IGHV) region or using IGHV3-21 (n = 10)...
February 12, 2019: Blood Advances
Naema Nayyar, Michael D White, Corey M Gill, Matthew Lastrapes, Mia Bertalan, Alexander Kaplan, Megan R D'Andrea, Ivanna Bihun, Andrew Kaneb, Jorg Dietrich, Judith A Ferry, Maria Martinez-Lage, Anita Giobbie-Hurder, Darrell R Borger, Fausto J Rodriguez, Matthew P Frosch, Emily Batchelor, Kaitlin Hoang, Benjamin Kuter, Sarah Fortin, Matthias Holdhoff, Daniel P Cahill, Scott Carter, Priscilla K Brastianos, Tracy T Batchelor
The genetic alterations that define primary central nervous system lymphoma (PCNSL) are incompletely elucidated, and the genomic evolution from diagnosis to relapse is poorly understood. We performed whole-exome sequencing (WES) on 36 PCNSL patients and targeted MYD88 sequencing on a validation cohort of 27 PCNSL patients. We also performed WES and phylogenetic analysis of 3 matched newly diagnosed and relapsed tumor specimens and 1 synchronous intracranial and extracranial relapse. Immunohistochemistry (IHC) for programmed death-1 ligand (PD-L1) was performed on 43 patient specimens...
February 12, 2019: Blood Advances
Naranie Shanmuganathan, Susan Branford, Timothy P Hughes, Devendra Hiwase
No abstract text is available yet for this article.
February 12, 2019: Blood Advances
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