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Haematologica

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https://www.readbyqxmd.com/read/29773604/transcriptional-activities-of-dux4-fusions-in-b-cell-acute-lymphoblastic-leukemia
#1
Yosuke Tanaka, Masahito Kawazu, Takahiko Yasuda, Miki Tamura, Fumihiko Hayakawa, Shinya Kojima, Toshihide Ueno, Hitoshi Kiyoi, Tomoki Naoe, Hiroyuki Mano
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773603/clinical-efficacy-of-ruxolitinib-and-chemotherapy-in-a-child-with-philadelphia-chromosome-like-acute-lymphoblastic-leukemia-with-golga5-jak2-fusion-and-induction-failure
#2
Yang Y Ding, Julie W Stern, Tracey F Jubelirer, Gerald B Wertheim, Fumin Li, Fengqi Chang, Zhaohui Gu, Charles G Mullighan, Yong Li, Richard C Harvey, I-Ming Chen, Cheryl L Willman, Stephen P Hunger, Marilyn M Li, Sarah K Tasian
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773602/clofarabine-high-dose-cytarabine-and-liposomal-daunorubicin-in-pediatric-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-study
#3
Natasha K A van Eijkelenburg, Mareike Rasche, Essam Ghazaly, Michael N Dworzak, Thomas Klingebiel, Claudia Rossig, Guy Leverger, Jan Stary, Eveline S J M de Bont, Dana A Chitu, Yves Bertrand, Benoit Brethon, Brigitte Strahm, Inge M van der Sluis, Gertjan J L Kaspers, Dirk Reinhardt, C Michel Zwaan
Survival in children with relapsed/refractory acute myeloid leukemia is unsatisfactory. Treatment consists of one course fludarabine, cytarabine and liposomal daunorubicin, followed by fludarabine and cytarabine and stem-cell transplantation. Study ITCC 020/I-BFM 2009-02 aimed to identify the recommended phase 2 dose of clofarabine replacing fludarabine in the abovementioned combination regimen (3+3 design). Escalating dose-levels of clofarabine (20-40mg/m2/day x5days) and liposomal daunorubicin (40-0mg/m2/day) were administered with cytarabine (2g/m2/day x5days)...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773601/combinatorial-targeting-of-xpo1-and-flt3-exerts-synergistic-anti-leukemia-effects-through-induction-of-differentiation-and-apoptosis-in-flt3-mutated-acute-myeloid-leukemias-from-concept-to-clinical-trial
#4
Weiguo Zhang, Charlie Ly, Jo Ishizawa, Hong Mu, Vivian Ruvolo, Sharon Shacham, Naval Daver, Michael Andreeff
Targeted therapies against FLT3-mutated acute myeloid leukemia have shown limited clinical efficacy primarily because of the acquisition of secondary mutations in FLT3 and persistent activation of downstream pro-survival pathways such as MEK/ERK, PI3K/AKT, and STAT5. Activation of these additional kinases may also result in phosphorylation of tumor suppressor proteins promoting their nuclear export. Thus, co-targeting nuclear export proteins (i.e., XPO1) and FLT3 concomitantly may be therapeutically effective...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773600/the-interleukin-3-receptor-cd123-targeted-sl-401-mediates-potent-cytotoxic-activity-against-cd34-cd123-cells-from-acute-myeloid-leukemia-myelodysplastic-syndrome-patients-and-healthy-donors
#5
Rajeswaran Mani, Swagata Goswami, Bhavani Gopalakrishnan, Rahul Ramaswamy, Ronni Wasmuth, Minh Tranh, Xiaokui Mo, Amber Gordon, Donna Bucci, David M Lucas, Alice Mims, Christopher Brooks, Adrienne Dorrance, Alison Walker, William Blum, John C Byrd, Gerard Lozanski, Sumithira Vasu, Natarajan Muthusamy
Diseases with clonal hematopoiesis such as myelodysplastic syndrome and acute myeloid leukemia have high rates of relapse. Only a small subset of acute myeloid leukemia patients are cured with chemotherapy alone. Relapse in these diseases occurs at least in part due to the failure to eradicate leukemic stem cells or hematopoietic stem cells in myelodysplastic syndrome. CD123, the alpha chain of the interleukin-3 receptor heterodimer, is expressed on the majority of leukemic stem cells and myelodysplastic syndrome hematopoietic stem cells and in 80% of acute myeloid leukemia...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773599/tgf%C3%AE-1-mediated-functional-inhibition-of-mesenchymal-stromal-cells-in-myelodysplastic-syndromes-and-acute-myeloid-leukemia
#6
Stefanie Geyh, Manuel Rodríguez-Paredes, Paul Jäger, Annemarie Koch, Felix Bormann, Julian Gutekunst, Christoph Zilkens, Ulrich Germing, Guido Kobbe, Frank Lyko, Rainer Haas, Thomas Schroeder
Mesenchymal stromal cells are involved in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia, but the underlying mechanisms are incompletely understood. To further characterize the pathological phenotype we performed RNA sequencing of mesenchymal stromal cells from patients with myelodysplastic syndromes and acute myeloid leukemia revealing a specific molecular signature of genes commonly deregulated in myelodysplastic syndromes and acute myeloid leukemia. Pathway analysis showed a strong enrichment of genes related to osteogenesis, senescence, inflammation and inhibitory cytokines thereby reflecting the structural and functional deficits of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia on a molecular level...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773598/concomitant-wt1-mutations-predict-poor-prognosis-in-acute-myeloid-leukemia-patients-with-double-mutant-cebpa
#7
Feng-Ming Tien, Hsin-An Hou, Jih-Luh Tang, Yuan-Yeh Kuo, Chien-Yuan Chen, Cheng-Hong Tsai, Ming Yao, Chien-Ting Lin, Chi-Cheng Li, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Shang-Ju Wu, Jia-Hau Liu, Sheng-Chieh Chou, Woei Tsay, Mei-Hsuan Tseng, Ming-Chih Liu, Chia-Wen Liu, Liang-In Lin, Wen-Chien Chou, Hwei-Fang Tien
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773597/hematopoietic-stem-cell-loss-and-hematopoietic-failure-in-severe-aplastic-anemia-is-driven-by-macrophages-and-aberrant-podoplanin-expression
#8
Amanda McCabe, Julianne N P Smith, Angelica Costello, Jackson Maloney, Divya Katikaneni, Katherine C MacNamara
Severe aplastic anemia results from profound hematopoietic stem cell loss. T cells and interferon gamma have long been associated with severe aplastic anemia, yet the underlying mechanisms driving hematopoietic stem cell loss remain unknown. Using a mouse model of severe aplastic anemia, we demonstrate that interferon gamma-dependent hematopoietic stem cell loss required macrophages. Interferon gamma was necessary for bone marrow macrophage persistence, despite loss of other myeloid cells and hematopoietic stem cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773596/card10-a-cebpe-target-involved-in-granulocytic-differentiation
#9
Pavithra Shyamsunder, Haresh Sankar, Anand Mayakonda, Lin Han, Hazimah Binte Mohd Nordin, Teoh Weoi Woon, Mahalakshmi Shanmugasundaram, Pushkar Dakle, Vikas Madan, H Phillip Koeffler
Maturation of granulocytes is dependent on controlled gene expression by myeloid lineage restricted transcription factors. CEBPE is one of the essential transcription factors required for granulocytic differentiation. Identification of downstream targets of CEBPE is vital to understand better its role in terminal granulopoiesis. In this study, we have identified Card10 as a novel target of CEBPE. We show that CEBPE binds to regulatory elements upstream of the murine Card10 locus, and expression of CARD10 is significantly reduced in Cebpe knock-out mice...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773595/therapeutic-effects-of-the-novel-subtype-selective-histone-deacetylase-hdac-inhibitor-chidamide-on-myeloma-associated-bone-disease
#10
Jingsong He, Qingxiao Chen, Huiyao Gu, Jing Chen, Enfan Zhang, Xing Guo, Xi Huang, Haimeng Yan, DongHua He, Yang Yang, Yi Zhao, Gang Wang, Huang He, Qing Yi, Zhen Cai
Histone deacetylases are promising therapeutic targets in hematological malignancies. In the present work, we investigated the effect of chidamide, a new subtype-selective histone deacetylase inhibitor that was independently produced in China, on multiple myeloma and its associated bone diseases using different models. The cytotoxicity of chidamide toward myeloma is due to its induction of cell apoptosis and cell cycle arrest by increasing the levels of caspase family proteins, including p21 and p27, among others...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773594/interleukin-22-levels-are-increased-in-gastrointestinal-graft-versus-host-disease-in-children
#11
Dana T Lounder, Pooja Khandelwal, Nicholas J Gloude, Christopher E Dandoy, Sonata Jodele, Mario Medvedovic, Lee A Denson, Adam Lane, Kelly Lake, Bridget Litts, Alyss Wilkey, Stella M Davies
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773593/safety-and-efficacy-of-second-line-bosutinib-for-chronic-phase-chronic-myeloid-leukemia-over-a-five-year-period-final-results-of-a-phase-1-2-study
#12
Carlo Gambacorti-Passerini, Jorge E Cortes, Jeff H Lipton, Hagop M Kantarjian, Dong-Wook Kim, Philippe Schafhausen, Rocco Crescenzo, Nathalie Bardy-Bouxin, Mark Shapiro, Kay Noonan, Eric Leip, Liza DeAnnuntis, Tim H Brümmendorf, H Jean Khoury
Bosutinib is a Src/Abl tyrosine kinase inhibitor indicated for adults with newly-diagnosed Ph+ chronic myeloid leukemia or with resistant/intolerant disease. We report the final results of a phase 1/2 study of second-line bosutinib in chronic phase chronic myeloid leukemia patients after imatinib failure (n=284). Median follow-up and treatment durations were 54.8 (range, 0.6-96.3) and 25.6 (0.2&-96.3) months, respectively. At years 2 and 5, 54% and 40% of patients, respectively, remained on bosutinib. Cumulative major cytogenetic response and complete cytogenetic response rates (newly-attained or maintained from baseline) were 58% and 46%, respectively, by year 2 and 60% and 50% by year 5...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773592/investigating-chemoresistance-to-improve-sensitivity-of-childhood-t-cell-acute-lymphoblastic-leukemia-to-parthenolide
#13
Benjamin C Ede, Rafal R Asmaro, John P Moppett, Paraskevi Diamanti, Allison Blair
Current therapies for childhood T cell acute lymphoblastic leukemia have increased survival rates to above 85% in developed countries. Unfortunately, some patients fail to respond to therapy and many suffer from serious side effects, highlighting the need to investigate other agents to treat this disease. Parthenolide, a nuclear factor kappa B inhibitor and reactive oxygen species inducer, has been shown to have excellent anti-cancer activity in pediatric leukemia xenografts, with minimal effects on normal hemopoietic cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773591/t-11-14-positive-mantel-cell-lymphomas-lacking-cyclin-d1-ccnd1-immunostaining-because-of-a-ccnd1-mutation-or-exclusive-expression-of-the-ccnd1b-isoform
#14
Ingram Iaccarino, Lamis Afify, Sietse M Aukema, Katharina Reddemann, Philipp Schütt, Martin Flür, Wolfram Klapper
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773590/impact-of-ibrutinib-dose-intensity-on-patient-outcomes-in-previously-treated-waldenstr%C3%A3-m-macroglobulinemia
#15
Jorge J Castillo, Joshua N Gustine, Kirsten Meid, Toni E Dubeau, Lian Xu, Guang Yang, Zachary R Hunter, Ranjana Advani, Lia Palomba, Steven P Treon
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29748447/morphologic-immunophenotypic-and-genetic-features-of-chronic-lymphocytic-leukemia-with-trisomy-12-a-comprehensive-review
#16
Francesco Autore, Paolo Strati, Luca Laurenti, Alessandra Ferrajoli
Chronic lymphocytic leukemia is an extremely heterogeneous disease and prognostic factors such as chromosomal abnormalities are important predictors of time to first treatment and survival. Trisomy 12 is the second most frequent aberration detected by fluorescence in situ hybridization at the time of diagnosis (10% to 25%), and it confers an intermediate prognostic risk, with a median time to first treatment of 33 months and a median overall survival of 114 months. Here, we review the unique morphologic, immunophenotypic, and genetic characteristics of patients with chronic lymphocytic leukemia and trisomy 12...
May 10, 2018: Haematologica
https://www.readbyqxmd.com/read/29748446/braf-v600e-mutation-detected-in-a-case-of-rosai-dorfman-disease
#17
Giancarlo Fatobene, Julien Haroche, Zofia Hélias-Rodzwicz, Frédéric Charlotte, Valérie Taly, Aliana Meneses Ferreira, André Néder Ramires Abdo, Vanderson Rocha, Jean-François Emile
No abstract text is available yet for this article.
May 10, 2018: Haematologica
https://www.readbyqxmd.com/read/29748445/grp94-rewires-and-buffers-the-flt3-itd-signaling-network-and-promotes-survival-of-acute-myeloid-leukemic-stem-cells
#18
Beibei Zhang, Pilar Ayuda Durán, Laure Piechaczyk, Yngvar Fløisand, Mireia Mayoral Safont Safont, Ida Tveit Karlsen, Zina Fandalyuk, Dagim Tadele, Pepijn van Mierlo, Alexander D Rowe, Joseph M Robertson, Bjørn Tore Gjertsen, Emmet McCormack, Jorrit M Enserink
Internal tandem duplications in the tyrosine kinase receptor FLT3 (FLT3-ITD) are among the most common lesions in acute myeloid leukemia and there exists a need for new forms of treatment. Using ex vivo drug sensitivity screening, we found that FLT3-ITD+ patient cells are particularly sensitive to HSP90 inhibitors. While it is well known that HSP90 is important for FLT3-ITD stability, we found that HSP90 family members play a much more complex role in FLT3-ITD signaling than previously appreciated. First, we found that FLT3-ITD activates the unfolded protein response, leading to increased expression of GRP94/HSP90B1...
May 10, 2018: Haematologica
https://www.readbyqxmd.com/read/29748444/rituximab-plus-bendamustine-as-front-line-treatment-in-frail-elderly-70-years-patients-with-diffuse-large-b-cell-non-hodgkin-s-lymphoma-a-phase-ii-multicenter-study-of-the-fondazione-italiana-linfomi
#19
Sergio Storti, Michele Spina, Emanuela Anna Pesce, Flavia Salvi, Michele Merli, Alessia Ruffini, Giuseppina Cabras, Annalisa Chiappella, Emanuele Angelucci, Alberto Fabbri, Anna Marina Liberati, Monica Tani, Gerardo Musuraca, Annalia Molinari, Maria Pia Petrilli, Carmela Palladino, Rosanna Ciancia, Andrea Ferrario, Cristiana Gasbarrino, Federico Monaco, Vincenzo Fraticelli, Annalisa De Vellis, Francesco Merli, Stefano Luminari
We conducted a phase II study to assess activity and safety profile of bendamustine and rituximab in elderly patients with untreated Diffuse Large B Cell Lymphoma who were prospectively defined as frail using a simplified version of a Comprehensive Geriatric Assessment. Patients had to be > 70 years of age, with histologically confirmed Diffuse Large B Cell Lymphoma. Frail patients were those younger than 80 years with a frail profile at Comprehensive Geriatric Assessment or older than 80 years with an unfit profile...
May 10, 2018: Haematologica
https://www.readbyqxmd.com/read/29748443/a-phase-2-multicenter-study-of-the-anti-cd19-antibody-drug-conjugate-coltuximab-ravtansine-sar3419-in-patients-with-relapsed-or-refractory-diffuse-large-b-cell-lymphoma-previously-treated-with-rituximab-based-immunotherapy
#20
Marek Trněný, Gregor Verhoef, Martin Js Dyer, Dina Ben Yehuda, Caterina Patti, Miguel Canales, Andrés Lopez, Farrukh T Awan, Paul G Montgomery, Andrea Janikova, Anna M Barbui, Kazimierz Sulek, Maria J Terol, John Radford, Anna Guidetti, Massimo Di Nicola, Laure Siraudin, Laurence Hatteville, Sandrine Schwab, Corina Oprea, Alessandro M Gianni
This phase 2, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented (de novo or transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab containing immuno-chemotherapy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥ lesion >5 cm) at trial entry...
May 10, 2018: Haematologica
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