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https://www.readbyqxmd.com/read/28522442/bcl2-expression-in-dlbcl-reappraisal-of-immunohistochemistry-with-new-criteria-for-therapeutic-biomarker-evaluation
#1
Naoko Tsuyama, Seiji Sakata, Satoko Baba, Yuko Mishima, Noriko Nishimura, Kyoko Ueda, Masahiro Yokoyama, Yasuhito Terui, Kiyohiko Hatake, Masanobu Kitagawa, Naoki Ishizuka, Naoto Tomita, Kengo Takeuchi
Overexpression of the BCL2 is associated with a poor prognosis in diffuse large B-cell lymphoma (DLBCL). The assessment of MYC immunohistochemistry (IHC) is becoming optimized, whereas the criteria for BCL2 positivity are highly variable. Furthermore, data on the frequency and prognostic value of BCL2 positivity are conflicting. We aimed to evaluate BCL2 expression by IHC and assess the prognostic significance of the histopathologically-scored BCL2 expression in 456 patients with DLBCL uniformly treated with standard immunochemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP)...
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28522441/encouraging-activity-for-r-chop-in-advanced-stage-nodular-lymphocyte-predominant-hodgkin-lymphoma
#2
Michelle A Fanale, Chan Yoon Cheah, Amy Rich, L Jeffrey Medeiros, Chao-Ming Lai, Yasuhiro Oki, Jorge E Romaguera, Luis Fayad, F B Hagemeister, Felipe Samaniego, Maria A Rodriguez, Sattva S Neelapu, Hun J Lee, Loretta Nastoupil, Nathan Fowler, Francesco Turturro, Jason Westin, Michael Wang, Peter McLaughlin, Chelsea Pinnix, Sarah Milgrom, Bouthaina Dabaja, Sandra B Horowitz, Anas Younes
Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized R-CHOP could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free (PFS), overall survival (OS) and histologic transformation according to treatment strategy and explorede prognostic factors for PFS and OS...
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28522440/dusp22-and-tp63-rearrangements-predict-outcome-of-alk-negative-anaplastic-large-cell-lymphoma-a-danish-cohort-study
#3
Martin Bjerregård Pedersen, Stephen Jacques Hamilton-Dutoit, Knud Bendix, Rhett P Ketterling, Patrick P Bedroske, Ivy M Luoma, Christopher A Sattler, Rebecca L Boddicker, N Nora Bennani, Peter Nørgaard, Michael Boe Møller, Torben Steiniche, Francesco d'Amore, Andrew L Feldman
No abstract text is available yet for this article.
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28515095/a-prognostic-index-for-chronic-and-smoldering-type-adult-t-cell-leukemia-lymphoma
#4
Hiroo Katsuya, Mototsugu Shimokawa, Kenji Ishitsuka, Kazuhiro Kawai, Masahiro Amano, Atae Utsunomiya, Ryosuke Hino, Shuichi Hanada, Tatsuro Jo, Kunihiro Tsukasaki, Yukiyoshi Moriuchi, Eisaburo Sueoka, Shinichiro Yoshida, Hitoshi Suzushima, Masaharu Miyahara, Kiyoshi Yamashita, Tetsuya Eto, Junji Suzumiya, Kazuo Tamura
Adult T-cell leukemia-lymphoma (ATL) has been divided into 4 clinical subtypes: acute, lymphoma, chronic, and smoldering. The aim of this study is to develop a novel prognostic index (PI) for chronic and smoldering ATL. We conducted a nationwide retrospective survey on ATL patients, and 248 fully eligible individuals were used in this analysis. In the univariate analysis, gender, performance status, log10[soluble interleukin-2 receptor (sIL-2R)], neutrophils count, and lymphadenopathy showed P values less than ...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28515094/inhibiting-the-osteocyte-specific-protein-sclerostin-increases-bone-mass-and-fracture-resistance-in-multiple-myeloma
#5
Michelle M McDonald, Michaela R Reagan, Scott E Youlten, Sindhu T Mohanty, Anja Seckinger, Rachael L Terry, Jessica A Pettitt, Marija K Simic, Tegan L Cheng, Alyson Morse, Lawrence M T Le, David Abi-Hanna, Ina Kramer, Carolyne Falank, Heather Fairfield, Irene M Ghobrial, Paul A Baldock, David G Little, Michaela Kneissel, Karin Vanderkerken, J H Duncan Bassett, Graham R Williams, Babatunde O Oyajobi, Dirk Hose, Tri G Phan, Peter I Croucher
Multiple myeloma is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Treatment with bisphosphonates, which inhibit bone resorption, prevents bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28515093/circulating-soluble-p-selectin-must-dimerize-to-promote-inflammation-and-coagulation-in-mice
#6
Sumith R Panicker, Padmaja Mehta-D'souza, Nan Zhang, Arkadiusz G Klopocki, Bojing Shao, Rodger P McEver
Leukocyte adhesion to P-selectin on activated platelets and endothelial cells induces shedding of the P-selectin ectodomain into the circulation. Plasma soluble P-selectin (sP-selectin) is elevated 3-4-fold in patients with cardiovascular disease. Circulating sP-selectin is thought to trigger signaling in leukocytes that directly contributes to inflammation and thrombosis. However, sP-selectin likely circulates as a monomer, and in vitro studies suggest that sP-selectin must dimerize to induce signaling in leukocytes...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28515092/human-cd62l-dim-neutrophils-identified-as-a-separate-subset-by-proteome-profiling-and-in-vivo-pulse-chase-labelling
#7
Tamar Tak, Patrick Wijten, Marjolein Heeres, Peter Pickkers, Arjen Scholten, Albert J R Heck, Nienke Vrisekoop, Luke P Leenen, Jos Eacute A M Borghans, Kiki Tesselaar, Leo Koenderman
During acute inflammation three neutrophil subsets are found in the blood: neutrophils with a conventional segmented nucleus, neutrophils with a banded nucleus and T-cell-suppressing CD62L(dim) neutrophils with a high number of nuclear lobes. In this study (clinicaltrials.gov NCT01766414) we compared the in vivo kinetics and proteomes of banded, mature and hypersegmented neutrophils to determine whether these cell types represent truly different neutrophil subsets or reflect changes induced by LPS activation...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28515091/angiotensin-converting-enzyme-enhances-the-oxidative-response-and-bactericidal-activity-of-neutrophils
#8
Zakir Khan, Xiao Z Shen, Ellen A Bernstein, Jorge F Giani, Masahiro Eriguchi, Tuantuan V Zhao, Romer A Gonzalez-Villalobos, Sebastien Fuchs, George Y Liu, Kenneth E Bernstein
Angiotensin converting enzyme (ACE) inhibitors are widely used to reduce blood pressure. Here, we examined if ACE is important for the antibacterial effectiveness of neutrophils. ACE knockout mice or mice treated with an ACE inhibitor were more susceptible to bacterial infection by methicillin-resistant S. aureus (MRSA). In contrast, mice over expressing ACE in neutrophils (Neu(ACE) mice) have increased resistance to MRSA, and better in vitro killing of MRSA, P. aeruginosa, and K. pneumoniae ACE overexpression increased neutrophil production of reactive oxygen species (ROS) following MRSA challenge, an effect independent of the angiotensin II AT1 receptor...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28515090/nf-%C3%AE%C2%BAb-p50-nfkb1-contributes-to-pathogenesis-in-the-e%C3%AE-tcl1-mouse-model-of-chronic-lymphocytic-leukemia
#9
Timothy L Chen, Minh Tran, Aparna Lakshmanan, Bonnie K Harrington, Virginia M Goettl, Amy M Lehman, Stephen Trudeau, David M Lucas, Amy J Johnson, John C Byrd, Erin Hertlein
No abstract text is available yet for this article.
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28512190/hematopoietic-origin-of-langerhans-cell-histiocytosis-and-erdheim-chester-disease-in-adults
#10
Paul Milne, Venetia Bigley, Chris M Bacon, Antoine Néel, Naomi McGovern, Simon Bomken, Muzlifah Haniffa, Eli L Diamond, Benjamin H Durham, Johannes Visser, David Hunt, Harsha Gunawardena, Mac Macheta, Kenneth L McClain, Carl Allen, Omar Abdel-Wahab, Matthew Collin
Langerhans cell histiocytosis (LCH) and Erdheim Chester Disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAP kinase pathway genes. BRAF(V600E) mutation is the most common mutation in both conditions and also occurs in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult LCH or ECD arise from hematopoietic stem cells (HSC) nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAF V600E allele-specific PCR was used to map the neoplastic clone in 20 adults with LCH ECD and HCL...
May 16, 2017: Blood
https://www.readbyqxmd.com/read/28507083/frequency-and-epitope-specificity-of-anti-factor-viii-c1-domain-antibodies-in-acquired-and-congenital-hemophilia-a
#11
Joerg Kahle, Aleksander Orlowski, Diana Stichel, John F Healey, Ernest T Parker, Marc Jaquemin, Manuela Krause, Andreas Tiede, Dirk Schwabe, Pete Lollar, Christoph Königs
Several studies showed that neutralizing anti-factor VIII (fVIII) antibodies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study the frequency and epitope specificity of anti-C1 antibodies were analyzed in acquired and congenital hemophilia inhibitor patients (n=178). The domain specificity of antibodies was studied by homologue-scanning mutagenesis (HSM) with single human domain human/porcine fVIII proteins and antibody binding to human A2, C1 and C2 domains presented as human serum albumin (HSA) fusion proteins...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28507082/association-between-diffuse-myocardial-fibrosis-and-diastolic-dysfunction-in-sickle-cell-anemia
#12
Omar Niss, Robert Fleck, Fowe Makue, Tarek Alsaied, Payal Desai, Jeffrey A Towbin, Punam Malik, Michael D Taylor, Charles T Quinn
Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic dysfunction and hyperdynamic features. Diastolic dysfunction portends early mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA is unknown. We used cardiac magnetic resonance (CMR) measurements of extracellular volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25 individuals with SCA (mean age 23±13 years), and determine the association between diffuse myocardial fibrosis and diastolic dysfunction...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28507081/reversion-of-anergy-signatures-in-clonal-cd21low-b-cells-of-mixed-cryoglobulinemia-after-clearance-of-hcv-viremia
#13
Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato, Marcella Visentini
Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM(+)CD27(+) B cells. These cells display both the features of anergy induced by continual engagement of the B cell receptor (BCR), such as high expression of phosphorylated extracellular signal regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion such as CD21(low) phenotype and defective response to ligation of BCR and Toll-like receptor 9 (TLR9). Usually MC regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28500171/platelet-microparticles-infiltrating-solid-tumors-transfer-mirnas-that-suppress-tumor-growth
#14
James V Michael, Jeremy G T Wurtzel, Guang Fen Mao, A Koneti Rao, Mikhail A Kolpakov, Abdelkarim Sabri, Nicholas E Hoffman, Sudarsan Rajan, Dhanendra Tomar, Muniswamy Madesh, Marvin T Nieman, Johnny Yu, Leonard C Edelstein, Jesse W Rowley, Andrew S Weyrich, Lawrence E Goldfinger
Platelet-derived microparticles (PMPs) are associated with enhancement of metastasis and poor cancer outcomes. Circulating PMPs transfer platelet microRNAs (miRNAs) to vascular cells. Solid tumor vasculature is highly permeable, allowing the possibility of PMP-tumor cell interaction. Here we show that PMPs infiltrate solid tumors in humans and mice and transfer platelet-derived RNA, including miRNAs, to tumor cells in vivo and in vitro, resulting in tumor cell apoptosis. MiR-24 was a major species in this transfer...
May 12, 2017: Blood
https://www.readbyqxmd.com/read/28500170/jak2-inhibitors-for-myeloproliferative-neoplasms-what-is-next
#15
Prithviraj Bose, Srdan Verstovsek
Since its approval in 2011, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib has evolved to become the centerpiece of therapy for myelofibrosis (MF), and its use in patients with hydroxyurea resistant/intolerant polycythemia vera (PV) is steadily increasing. A number of other JAK2 inhibitors have entered clinical testing, but none has been approved yet, and many discontinued. Importantly, the activity of these agents is not restricted to patients with JAK2 V617F or exon 12 mutations. Although JAK2 inhibitors provide substantial clinical benefit, their disease-modifying activity is limited, and rational combinations with other targeted agents are needed, particularly in MF, where survival is short...
May 12, 2017: Blood
https://www.readbyqxmd.com/read/28495794/an-endpoint-associated-with-clinical-benefit-after-initial-treatment-for-chronic-graft-versus-host-disease
#16
Paul J Martin, Barry E Storer, Yoshihiro Inamoto, Mary E D Flowers, Paul A Carpenter, Joseph Pidala, Jeanne Palmer, Mukta Arora, Madan Jagasia, Sally Arai, Corey Cutler, Stephanie J Lee
No gold standard has been established as a primary endpoint in trials of initial treatment for chronic graft-versus-host disease (GVHD), and evidence showing the association of any proposed primary endpoint with clinical benefit has not been conclusively demonstrated. To address this gap, we analyzed outcomes in a cohort of 328 patients enrolled in a prospective, multicenter, observational study within 3 months after diagnosis of chronic GVHD. Complete and partial response, stable disease and progressive disease were defined according to the 2014 NIH Consensus Development Conference on Criteria for Clinical Trials in Chronic Graft-versus-host Disease...
May 11, 2017: Blood
https://www.readbyqxmd.com/read/28495793/usp7-inhibition-alters-homologous-recombination-repair-and-targets-cll-cells-independent-of-atm-p53-functional-status
#17
Angelo Agathanggelou, Edward Smith, Nicholas J Davies, Marwan Kwok, Anastasia Zlatanou, Ceri E Oldreive, Jingwen Mao, David Da Costa, Sina Yadollahi, Tracey Perry, Pamela Kearns, Anna Skowronska, Elliot Yates, Helen Parry, Peter Hillmen, Celine Reverdy, Remi Delansorne, Shankara Paneesha, Guy Pratt, Paul Moss, A Malcolm R Taylor, Grant S Stewart, Tatjana Stankovic
The role of the deubiquitylase ubiquitin-specific protease 7 (USP7) in the regulation of the p53-dependent DNA damage response (DDR) pathway is well established. Whilst previous studies have mostly focused on the mechanisms underlying how USP7 directly controls p53 stability, we have recently shown that USP7 modulates the stability of the DNA damage responsive E3 ubiquitin ligase, RAD18. This suggests that targeting USP7 may have therapeutic potential even in tumors with defective p53 or ibrutinib resistance...
May 11, 2017: Blood
https://www.readbyqxmd.com/read/28495792/cd70-reverse-signaling-enhances-nk-cell-function-and-immunosurveillance-in-cd27-expressing-b-cell-malignancies
#18
Mohamad F Al Sayed, Carla A Ruckstuhl, Tamara Hilmenyuk, Christina Claus, Jean-Pierre Bourquin, Beat C Bornhauser, Ramin Radpour, Carsten Riether, Adrian F Ochsenbein
The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells (Tregs). Similar to other TNFR-ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B cell non-Hodgkin lymphoma (NHL), but its role in the immune control of lymphoma and leukemia is unknown...
May 11, 2017: Blood
https://www.readbyqxmd.com/read/28490572/heterogeneous-resistance-to-quizartinib-in-acute-myeloid-leukemia-aml-revealed-by-single-cell-analysis
#19
Catherine C Smith, Amy Paguirigan, Grace R Jeschke, Kimberly C Lin, Evan Massi, Theodore Tarver, Chen-Shan Chin, Saurabh Asthana, Adam Olshen, Kevin J Travers, Susana Wang, Mark J Levis, Alexander E Perl, Jerald P Radich, Neil P Shah
Genomic studies have revealed significant branching heterogeneity in cancer. Studies of resistance to tyrosine kinase inhibitor (TKI) therapy have not fully reflected this heterogeneity as resistance in individual patients has been ascribed to largely mutually exclusive "on-target" or "off-target" mechanisms in which tumors either retain dependency on the target oncogene or subvert it through a parallel pathway. Using targeted sequencing from single cells and colonies from patient samples, we demonstrate tremendous clonal diversity in the majority of acute myeloid leukemia (AML) patients with activating FLT3 internal tandem duplication (ITD) mutations at the time of acquired resistance to the FLT3 inhibitor quizartinib...
May 10, 2017: Blood
https://www.readbyqxmd.com/read/28490571/evaluating-a-cll-susceptibility-variant-in-itgb2-in-families-with-multiple-sub-types-of-hematological-malignancies
#20
Nicholas B Blackburn, James R Marthick, Annette Banks, Jac C Charlesworth, Katherine A Marsden, Ray M Lowenthal, John Blangero, Joanne L Dickinson
No abstract text is available yet for this article.
May 10, 2017: Blood
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