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Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K

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https://www.readbyqxmd.com/read/29789652/small-hypoxia-primed-mesenchymal-stem-cells-attenuate-graft-versus-host-disease
#1
YongHwan Kim, Hye Jin Jin, Jinbeom Heo, Hyein Ju, Hye-Yeon Lee, Sujin Kim, Seungun Lee, Jisun Lim, Sang Young Jeong, JiHye Kwon, Miyeon Kim, Soo Jin Choi, Wonil Oh, Yoon Sun Yang, Hyun Ho Hwang, Hwan Yeul Yu, Chae-Min Ryu, Hong Bae Jeon, Dong-Myung Shin
Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation...
May 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29789651/analysis-of-the-genomic-landscape-of-multiple-myeloma-highlights-novel-prognostic-markers-and-disease-subgroups
#2
Niccolo Bolli, Giulia Biancon, Matahi Moarii, Silvia Gimondi, Yilong Li, Chiara de Philippis, Francesco Maura, Vijitha Sathiaseelan, Yu-Tzu Tai, Laura Mudie, Sarah O'Meara, Keiran Raine, Jon W Teague, Adam P Butler, Cristiana Carniti, Moritz Gerstung, Tina Bagratuni, Efstathios Kastritis, Meletios Dimopoulos, Paolo Corradini, Kenneth C Anderson, Philippe Moreau, Stephane Minvielle, Peter J Campbell, Elli Papaemmanuil, Herve Avet-Loiseau, Nikhil C Munshi
In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene...
May 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29740160/new-therapeutic-opportunities-from-dissecting-the-pre-b-leukemia-bone-marrow-microenvironment
#3
Laurence C Cheung, Jennifer Tickner, Anastasia M Hughes, Patrycja Skut, Meegan Howlett, Bree Foley, Joyce Oommen, Julia E Wells, Bo He, Sajla Singh, Grace-Alyssa Chua, Jette Ford, Charles G Mullighan, Rishi S Kotecha, Ursula R Kees
The microenvironments of leukemia and cancer are critical for multiple stages of malignancies, and they are an attractive therapeutic target. While skeletal abnormalities are commonly seen in children with acute lymphoblastic leukemia (ALL) prior to initiating osteotoxic therapy, little is known about the alterations to the bone marrow microenvironment during leukemogenesis. Therefore, in this study, we focused on the development of precursor-B cell ALL (pre-B ALL) in an immunocompetent BCR-ABL1+ model. Here we show that hematopoiesis was perturbed, B lymphopoiesis was impaired, collagen production was reduced, and the number of osteoblastic cells was decreased in the bone marrow microenvironment...
May 8, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29720735/prevention-and-management-of-adverse-events-of-novel-agents-in-multiple-myeloma-a-consensus-of-the-european-myeloma-network
#4
REVIEW
Heinz Ludwig, Michel Delforge, Thierry Facon, Hermann Einsele, Francesca Gay, Philippe Moreau, Hervé Avet-Loiseau, Mario Boccadoro, Roman Hajek, Mohamad Mohty, Michele Cavo, Meletios A Dimopoulos, Jesús F San-Miguel, Evangelos Terpos, Sonja Zweegman, Laurent Garderet, María-Victoria Mateos, Gordon Cook, Xavier Leleu, Hartmut Goldschmidt, Graham Jackson, Martin Kaiser, Katja Weisel, Niels W C J van de Donk, Anders Waage, Meral Beksac, Ulf H Mellqvist, Monika Engelhardt, Jo Caers, Christoph Driessen, Joan Bladé, Pieter Sonneveld
During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events...
May 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29749403/obinutuzumab-plus-bendamustine-in-previously-untreated-patients-with-cll-a-subgroup-analysis-of-the-green-study
#5
Stephan Stilgenbauer, Veronique Leblond, Robin Foà, Sebastian Böttcher, Osman Ilhan, Wolfgang Knauf, Eva Mikuskova, Christoph Renner, Eugen Tausch, Dariusz Woszczyk, Ekaterina Gresko, Linda Lundberg, Tom Moore, Thea Morris, Susan Robson, Francesc Bosch
GREEN (NCT01905943) is a non-randomized, open-label phase IIIb study investigating obinutuzumab alone or plus chemotherapy in chronic lymphocytic leukemia (CLL). We report a preplanned subgroup analysis of 158 previously untreated CLL patients receiving obinutuzumab-bendamustine (G-B). Patients received six 28-day cycles (C) of G-B: obinutuzumab day (D)1/D2 of C1 (25 mg D1/975 mg D2), 1000 mg D8 and D15 of C1, and D1 of C2-6; and bendamustine 70/90 mg/m2 D1 and D2 of C1-6. The primary endpoint was safety/tolerability...
April 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29784907/a-predictive-model-for-risk-of-early-grade-%C3%A2-3-infection-in-patients-with-multiple-myeloma-not-eligible-for-transplant-analysis-of-the-first-trial
#6
Charles Dumontet, Cyrille Hulin, Meletios A Dimopoulos, Andrew Belch, Angela Dispenzieri, Heinz Ludwig, Philippe Rodon, Jan Van Droogenbroeck, Lugui Qiu, Michele Cavo, Ann Van de Velde, Juan José Lahuerta, Olivier Allangba, Jae Hoon Lee, Eileen Boyle, Aurore Perrot, Philippe Moreau, Salomon Manier, Michel Attal, Murielle Roussel, Mohamad Mohty, Jean Yves Mary, Alexandre Civet, Bruno Costa, Antoine Tinel, Yann Gaston-Mathé, Thierry Facon
Infections are a major cause of death in patients with multiple myeloma. A post hoc analysis of the phase 3 FIRST trial was conducted to characterize treatment-emergent (TE) infections and study risk factors for TE grade ≥ 3 infection. The number of TE infections/month was highest during the first 4 months of treatment (defined as early infection). Of 1613 treated patients, 340 (21.1%) experienced TE grade ≥ 3 infections in the first 18 months and 56.2% of these patients experienced their first grade ≥ 3 infection in the first 4 months...
April 26, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29749402/clonal-piga-mosaicism-and-dynamics-in-paroxysmal-nocturnal-hemoglobinuria
#7
Michael J Clemente, Bartlomiej Przychodzen, Cassandra M Hirsch, Yasunobu Nagata, Taha Bat, Marcin W Wlodarski, Tomas Radivoyevitch, Hideki Makishima, Jaroslaw P Maciejewski
No abstract text is available yet for this article.
April 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29749401/blast-phase-chronic-myelomonocytic-leukemia-mayo-mdacc-collaborative-study-of-171-cases
#8
Mrinal M Patnaik, Ana A Pierola, Rangit Vallapureddy, Fevzi F Yalniz, Tapan M Kadia, Elias J Jabbour, Terra Lasho, Curtis A Hanson, Rhett P Ketterling, Hagop M Kantarjian, Ayalew Tefferi, Guillermo Garcia-Manero
No abstract text is available yet for this article.
April 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29743725/ufd1-contributes-to-myc-mediated-leukemia-aggressiveness-through-suppression-of-the-proapoptotic-unfolded-protein-response
#9
L N Huiting, Y Samaha, G L Zhang, J E Roderick, B Li, N M Anderson, Y W Wang, L Wang, Fjf Laroche, J W Choi, C T Liu, M A Kelliher, H Feng
Despite the pivotal role of MYC in tumorigenesis, the mechanisms by which it promotes cancer aggressiveness remain incompletely understood. Here, we show that MYC transcriptionally upregulates the ubiquitin fusion degradation 1 (UFD1) gene in T-cell acute lymphoblastic leukemia (T-ALL). Allelic loss of ufd1 in zebrafish induces tumor cell apoptosis and impairs MYC-driven T-ALL progression but does not affect general health. As the E2 component of an endoplasmic reticulum (ER)-associated degradation (ERAD) complex, UFD1 facilitates the elimination of misfolded/unfolded proteins from the ER...
April 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29743724/jak-map-kinase-pathway-activation-and-tp53-mutations-in-acute-leukemia-with-megakaryocytic-and-erythroid-differentiation
#10
Wenbin Xiao, Raajit Rampal, Yanming Zhang, Robert Cimera, Achim A Jungbluth, Maria Arcila, Mikhail Roshal, David C Park
No abstract text is available yet for this article.
April 24, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29743723/dysregulation-of-ezh2-mir-138-axis-contributes-to-drug-resistance-in-multiple-myeloma-by-downregulating-rbpms
#11
Nasrin Rastgoo, Maryam Pourabdollah, Jahangir Abdi, Donna Reece, Hong Chang
EZH2 is highly expressed in multiple myeloma (MM). However, the molecular mechanisms underlying EZH2 overexpression and its role in drug resistance of MM remain undefined. Here we show that EZH2 is upregulated in drug-resistant MM cells and its aberrant overexpression is associated with poor prognosis of MM patients. Overexpression of EZH2 in parental MM cells renders them resistant to anti-myeloma drugs and suppression of EZH2 displays the opposite effects. Using miRNA target scan algorithms, we identify miR-138 as a regulator of EZH2, which is conversely repressed by EZH2-induced H3K27 trimethylation in MM-resistant cell lines and primary tumor cells...
April 24, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29743722/management-of-patients-with-acute-promyelocytic-leukemia
#12
REVIEW
Sabine Kayser, Richard F Schlenk, Uwe Platzbecker
With the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) acute promyelocytic leukemia (APL) has become from a detrimental to one of the most curable malignant diseases in humans. In particular, the chemotherapy-free regimen with ATO/ATRA has been proven to be highly effective in de novo APL and has become standard first-line therapy in younger adult, non-high-risk patients. Nevertheless, early death is still a major issue in APL, particularly in older patients, emphasizing the need of rapid diagnostics and supportive care together with immediate access to ATRA-based therapy...
April 24, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29674643/diagnostic-thresholds-for-free-light-chains-in-multiple-myeloma-depend-on-the-assay-used
#13
Xavier Bossuyt, Michel Delforge, Martin Reynders, Doreen Dillaerts, Ben Sprangers, Karel Fostier, Koen Poesen, Martine Vercammen
No abstract text is available yet for this article.
April 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29749400/gata2-monoallelic-expression-underlies-reduced-penetrance-in-inherited-gata2-mutated-mds-aml
#14
Ahad F Al Seraihi, Ana Rio-Machin, Kiran Tawana, Csaba Bödör, Jun Wang, Ai Nagano, James A Heward, Sameena Iqbal, Steven Best, Nicholas Lea, Donal McLornan, Emilia J Kozyra, Marcin W Wlodarski, Charlotte M Niemeyer, Hamish Scott, Chris Hahn, Alicia Ellison, Hemanth Tummala, Shirleny Romualdo Cardoso, Tom Vulliamy, Inderjeet Dokal, Tom Butler, Matthew Smith, Jamie Cavenagh, Jude Fitzgibbon
No abstract text is available yet for this article.
April 19, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29743721/validation-of-the-eutos-long-term-survival-score-in-a-recent-independent-cohort-of-real-world-cml-patients
#15
Inge G P Geelen, Fredrik Sandin, Noortje Thielen, Jeroen J W M Janssen, Mels Hoogendoorn, Otto Visser, Jan J Cornelissen, Martin Hoglund, Peter E Westerweel
No abstract text is available yet for this article.
April 19, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29749399/autocrine-tnf-signaling-favors-malignant-cells-in-myelofibrosis-in-a-tnfr2-dependent-fashion
#16
William L Heaton, Anna V Senina, Anthony D Pomicter, Mohamed E Salama, Phillip M Clair, Dongqing Yan, Russell N Bell, Jeremy M Gililland, Josef T Prchal, Thomas O'Hare, Michael W Deininger
Tumor necrosis factor alpha (TNF) is increased in myelofibrosis (MF) and promotes survival of malignant over normal cells. The mechanisms altering TNF responsiveness in MF cells are unknown. We show that the proportion of marrow (BM) cells expressing TNF is increased in MF compared to controls, with the largest differential in primitive cells. Blockade of TNF receptor 2 (TNFR2), but not TNFR1, selectively inhibited colony formation by MF CD34+ and mouse JAK2V617F progenitor cells. Microarray of mouse MPN revealed reduced expression of X-linked inhibitor of apoptosis (Xiap) and mitogen-activated protein kinase 8 (Mapk8) in JAK2V617F relative to JAK2WT cells, which were normalized by TNFR2 but not TNFR1 blockade...
April 18, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29749398/cell-of-origin-dictates-aggression-and-stem-cell-number-in-acute-lymphoblastic-leukemia
#17
Elaine G Garcia, Sowmya Iyer, Sara P Garcia, Siebe Loontiens, Ruslan I Sadreyev, Frank Speleman, David M Langenau
No abstract text is available yet for this article.
April 18, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29740159/genetic-analysis-of-therapy-related-myeloid-neoplasms-occurring-after-intensive-treatment-for-acute-promyelocytic-leukemia
#18
Aline Renneville, Philippe Attias, Xavier Thomas, Cécile Bally, Sandrine Hayette, Hassan Farhat, Virginie Eclache, Alice Marceau-Renaut, Bruno Cassinat, Jean Feuillard, Christine Terré, Eric Delabesse, Sophie Park, Julie Lejeune, Sylvie Chevret, Lionel Adès, Claude Preudhomme, Pierre Fenaux
No abstract text is available yet for this article.
April 18, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29740158/single-cell-sequencing-reveals-the-origin-and-the-order-of-mutation-acquisition-in-t-cell-acute-lymphoblastic-leukemia
#19
Jolien De Bie, Sofie Demeyer, Llucia Alberti-Servera, Ellen Geerdens, Heidi Segers, Michaël Broux, Kim De Keersmaecker, Lucienne Michaux, Peter Vandenberghe, Thierry Voet, Nancy Boeckx, Anne Uyttebroeck, Jan Cools
Next-generation sequencing has provided a detailed overview of the various genomic lesions implicated in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). Typically, 10-20 protein-altering lesions are found in T-ALL cells at diagnosis. However, it is currently unclear in which order these mutations are acquired and in which progenitor cells this is initiated. To address these questions, we used targeted single-cell sequencing of total bone marrow cells and CD34+ CD38- multipotent progenitor cells for four T-ALL cases...
April 18, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29769624/serial-minimal-residual-disease-mrd-monitoring-during-first-line-fcr-treatment-for-cll-may-direct-individualized-therapeutic-strategies
#20
Philip A Thompson, Christine B Peterson, Paolo Strati, Jeff Jorgensen, Michael J Keating, Susan M O'Brien, Alessandra Ferrajoli, Jan A Burger, Zeev Estrov, Nitin Jain, Tapan M Kadia, Gautam Borthakur, Courtney D DiNardo, Naval Daver, Elias Jabbour, William G Wierda
Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end of therapy (EOT) in bone marrow using 4-color flow cytometry (sensitivity 10-4 ). Eighteen percent of patients had U-MRD after C3 and 48% at EOT...
April 17, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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