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

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https://read.qxmd.com/read/30760870/runx-proteins-desensitize-multiple-myeloma-to-lenalidomide-via-protecting-ikzfs-from-degradation
#1
Nan Zhou, Alvaro Gutierrez-Uzquiza, Xiang Yu Zheng, Renxu Chang, Dan T Vogl, Alfred L Garfall, Luca Bernabei, Anita Saraf, Laurence Florens, Michael P Washburn, Anuradha Illendula, John H Bushweller, Luca Busino
Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3) are transcription factors that promote multiple myeloma (MM) proliferation. The immunomodulatory imide drug (IMiD) lenalidomide promotes myeloma cell death via Cereblon (CRBN)-dependent ubiquitylation and proteasome-dependent degradation of IKZF1 and IKZF3. Although IMiDs have been used as first-line drugs for MM, the overall survival of refractory MM patients remains poor and demands the identification of novel agents to potentiate the therapeutic effect of IMiDs...
February 13, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30760869/genetic-mechanisms-of-primary-chemotherapy-resistance-in-pediatric-acute-myeloid-leukemia
#2
Nicole A McNeer, John Philip, Heather Geiger, Rhonda E Ries, Vincent-Philippe Lavallée, Michael Walsh, Minita Shah, Kanika Arora, Anne-Katrin Emde, Nicolas Robine, Todd A Alonzo, E Anders Kolb, Alan S Gamis, Malcolm Smith, Daniela Se Gerhard, Jaime Guidry-Auvil, Soheil Meshinchi, Alex Kentsis
Acute myeloid leukemias (AML) are characterized by mutations of tumor suppressor and oncogenes, involving distinct genes in adults and children. While certain mutations have been associated with the increased risk of AML relapse, the genomic landscape of primary chemotherapy-resistant AML is not well defined. As part of the TARGET initiative, we performed whole-genome DNA and transcriptome RNA and miRNA sequencing analysis of pediatric AML with failure of induction chemotherapy. We identified at least three genetic groups of patients with induction failure, including those with NUP98 rearrangements, somatic mutations of WT1 in the absence of apparent NUP98 mutations, and additional recurrent variants including those in KMT2C and MLLT10...
February 13, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30755708/ezh2-is-overexpressed-in-transitional-preplasmablasts-and-is-involved-in-human-plasma-cell-differentiation
#3
Laurie Herviou, Michel Jourdan, Anne-Marie Martinez, Giacomo Cavalli, Jerome Moreaux
Plasma cells (PCs) play a major role in the defense of the host organism against pathogens. We have shown that PC generation can be modeled using multi-step culture systems that reproduce the sequential cell differentiation occurring in vivo. Using this unique model, we investigated the role of EZH2 during PC differentiation (PCD) using H3K27me3 and EZH2 ChIP-binding profiles. We then studied the effect of the inhibition of EZH2 enzymatic activity to understand how EZH2 regulates the key functions involved in PCD...
February 12, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30755707/destabilization-of-aetfc-through-c-ebp%C3%AE-mediated-repression-of-lyl1-contributes-to-t-8-21-leukemic-cell-differentiation
#4
LETTER
Meng-Meng Zhang, Na Liu, Yuan-Liang Zhang, Bowen Rong, Xiao-Lin Wang, Chun-Hui Xu, Yin-Yin Xie, Shuhong Shen, Jiang Zhu, Stephen D Nimer, Zhu Chen, Sai-Juan Chen, Robert G Roeder, Fei Lan, Lan Wang, Qiu-Hua Huang, Xiao-Jian Sun
No abstract text is available yet for this article.
February 12, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30755706/gata1-epigenetic-deregulation-contributes-to-the-development-of-aml-with-npm1-and-flt3-itd-cooperating-mutations
#5
LETTER
Paolo Sportoletti, Letizia Celani, Emanuela Varasano, Roberta Rossi, Daniele Sorcini, Chiara Rompietti, Francesca Strozzini, Beatrice Del Papa, Valerio Guarente, Giulio Spinozzi, Debora Cecchini, Oxana Bereshchenko, Torsten Haferlach, Maria Paola Martelli, Franca Falzetti, Brunangelo Falini
No abstract text is available yet for this article.
February 12, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30737486/s100a9-induced-overexpression-of-pd-1-pd-l1-contributes-to-ineffective-hematopoiesis-in-myelodysplastic-syndromes
#6
Pinyang Cheng, Erika A Eksioglu, Xianghong Chen, Wendy Kandell, Thu Le Trinh, Ling Cen, Jin Qi, David A Sallman, Yu Zhang, Nhan Tu, William A Adams, Chunze Zhang, Jinhong Liu, John L Cleveland, Alan F List, Sheng Wei
Myelodysplastic syndromes (MDS) are characterized by dysplastic and ineffective hematopoiesis that can result from aberrant expansion and activation of myeloid-derived suppressor cells (MDSCs) within the bone marrow (BM) niche. MDSCs produce S100A9, which mediates premature death of hematopoietic stem and progenitor cells (HSPCs). The PD-1/PD-L1 immune checkpoint impairs immune responses by inducing T-cell exhaustion and apoptosis, but its role in MDS is uncharacterized. Here we report an increased expression of PD-1 on HSPCs and PD-L1 on MDSCs in MDS versus healthy donors, and that this checkpoint is also activated in S100A9 transgenic (S100A9Tg) mice, and by treatment of BM mononuclear cells (BM-MNC) with S100A9...
February 8, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30737485/prognostic-restaging-at-the-time-of-second-line-therapy-in-patients-with-al-amyloidosis
#7
Yi L Hwa, Morie A Gertz, Shaji K Kumar, Martha Q Lacy, Francis K Buadi, David Dingli, Prashant Kapoor, Steve R Zeldenrust, Nelson Leung, Susanne R Hayman, Wilson I Gonsalves, Taxiarchis V Kourelis, Rahma Warsame, Ronald S Go, Eli Muchtar, Miriam A Hobbs, Amie L Fonder, Stephen Russell, Robert A Kyle, S Vincent Rajkumar, Angela Dispenzieri
It is well known that staging of patients with AL amyloidosis at diagnosis predicts for survival, but there is a paucity of literature delineating the prognostic value of these systems at relapse. We evaluated the prognostic value of AL staging among 413 patients initiated with second-line therapy between 2000 and 2015. Both the Revised Mayo 2012 and the European revision of Mayo 2004 staging systems were used. The median time from initial treatment to second-line therapy was 11.7 months. The first-line therapy was autologous stem cell transplant (ASCT) in 179 (43%) patients and non-ASCT therapies in 234 patients...
February 8, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30737484/genome-wide-association-study-of-monoclonal-gammopathy-of-unknown-significance-mgus-comparison-with-multiple-myeloma
#8
LETTER
Hauke Thomsen, Subhayan Chattopadhyay, Niels Weinhold, Pavel Vodicka, Ludmila Vodickova, Per Hoffmann, Markus M Nöthen, Karl-Heinz Jöckel, Christian Langer, Roman Hajek, Göran Hallmans, Ulrika Pettersson-Kymmer, Claes Ohlsson, Florentin Späth, Richard Houlston, Hartmut Goldschmidt, Kari Hemminki, Asta Försti
No abstract text is available yet for this article.
February 8, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30737483/the-mechanistic-study-behind-suppression-of-gvhd-while-retaining-gvl-activities-by-myeloid-derived-suppressor-cells
#9
Jilu Zhang, Hui-Ming Chen, Ge Ma, Zuping Zhou, David Raulet, Andreana L Rivera, Shu-Hsia Chen, Ping-Ying Pan
Graft-versus-host disease (GVHD) is a major barrier to the widespread use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating hematologic malignancies. Myeloid-derived suppressor cells (MDSCs) have been recognized as crucial immunosuppressive cells in various pathologic settings. Here, we investigated whether the unique functional properties of MDSCs could be harnessed to control allo-HSCT-associated GVHD. Using multiple murine GVHD/GVL models including both MHC-mismatched and miHA-mismatched, we demonstrated that treatment with CD115+ MDSCs efficiently suppressed GVHD but did not significantly impair graft-versus-leukemia (GVL) activity, leading to 80 and 67% protection in treated mice in GVHD and GVL models, respectively...
February 8, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30737482/complex-karyotype-in-de-novo-acute-myeloid-leukemia-typical-and-atypical-subtypes-differ-molecularly-and-clinically
#10
Krzysztof Mrózek, Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Andrew J Carroll, Christopher J Walker, Deedra Nicolet, James S Blachly, Marius Bill, Dimitrios Papaioannou, Eunice S Wang, Geoffrey L Uy, Jonathan E Kolitz, Bayard L Powell, William Blum, Richard M Stone, John C Byrd, Clara D Bloomfield
Complex karyotype (CK) with ≥ 3 abnormalities is detected in 10-12% of patients with acute myeloid leukemia (AML) and associated with poor prognosis. The most common unbalanced abnormalities found in CK result in loss of material from the 5q, 7q, and/or 17p chromosome arms. The presence of 5q, 7q, and/or 17p abnormalities denotes typical CK and their absence denotes atypical CK. Since molecular features of CK-AML are not well characterized, we investigated mutational status of 81 leukemia/cancer-associated genes in 160 clinically well-characterized patients...
February 8, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30728457/randomized-phase-ii-trial-evaluating-induction-therapy-with-idarubicin-and-etoposide-plus-sequential-or-concurrent-azacitidine-and-maintenance-therapy-with-azacitidine
#11
R F Schlenk, D Weber, W Herr, G Wulf, H R Salih, H G Derigs, A Kuendgen, M Ringhoffer, B Hertenstein, U M Martens, M Grießhammer, H Bernhard, J Krauter, M Girschikofsky, D Wolf, E Lange, J Westermann, E Koller, S Kremers, M Wattad, M Heuser, F Thol, G Göhring, D Haase, V Teleanu, V Gaidzik, A Benner, K Döhner, A Ganser, P Paschka, H Döhner
The aim of this randomized phase-II study was to evaluate the effect of substituting cytarabine by azacitidine in intensive induction therapy of patients with acute myeloid leukemia (AML). Patients were randomized to four induction schedules for two cycles: STANDARD (idarubicin, cytarabine, etoposide); and azacitidine given prior (PRIOR), concurrently (CONCURRENT), or after (AFTER) therapy with idarubicin and etoposide. Consolidation therapy consisted of allogeneic hematopoietic-cell transplantation or three courses of high-dose cytarabine followed by 2-year maintenance therapy with azacitidine in the azacitidine-arms...
February 6, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30728456/data-mining-for-mutation-specific-targets-in-acute-myeloid-leukemia
#12
REVIEW
Brooks Benard, Andrew J Gentles, Thomas Köhnke, Ravindra Majeti, Daniel Thomas
Three mutation-specific targeted therapies have recently been approved by the FDA for the treatment of acute myeloid leukemia (AML): midostaurin for FLT3 mutations, enasidenib for relapsed or refractory cases with IDH2 mutations, and ivosidenib for cases with an IDH1 mutation. Together, these agents offer a mutation-directed treatment approach for up to 45% of de novo adult AML cases, a welcome deluge after a prolonged drought. At the same time, a number of computational tools have recently been developed that promise to further accelerate progress in mutation-specific therapy for AML and other cancers...
February 6, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30723257/peripheral-blood-minimal-measurable-residual-disease-assessed-in-flow-cytometry-in-acute-myeloblastic-leukemia
#13
LETTER
Cécile Guénot, Francis Lacombe, Kaoutar Allou, Florent Dumezy, Jean Feuillard, Franck Geneviève, Estelle Guérin, Julien Guy, Marc Maynadié, Orianne Wagner Ballon, Claude Preudhomme, André Baruchel, Hervé Dombret, Norbert Ifrah, Marie C Béné
No abstract text is available yet for this article.
February 5, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30718771/cytokine-production-in-myelofibrosis-exhibits-differential-responsiveness-to-jak-stat-map-kinase-and-nf%C3%AE%C2%BAb-signaling
#14
Daniel A C Fisher, Cathrine A Miner, Elizabeth K Engle, Hengrui Hu, Taylor B Collins, Amy Zhou, Maggie J Allen, Olga N Malkova, Stephen T Oh
The distinct clinical features of myelofibrosis (MF) have been attributed in part to dysregulated inflammatory cytokine production. Circulating cytokine levels are elevated in MF patients; a subset of which have been shown to be poor prognostic indicators. In this study, cytokine overproduction was examined in MF patient plasma and in MF blood cells ex vivo using mass cytometry. Plasma cytokines measured following treatment with ruxolitinib remained markedly abnormal, indicating that aberrant cytokine production persists despite therapeutic JAK2 inhibition...
February 4, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30705411/a-novel-method-for-detecting-the-cellular-stemness-state-in-normal-and-leukemic-human-hematopoietic-cells-can-predict-disease-outcome-and-drug-sensitivity
#15
Muhammad Yassin, Nasma Aqaqe, Abed Alkader Yassin, Peter van Galen, Eitan Kugler, Bradley E Bernstein, Maya Koren-Michowitz, Jonathan Canaani, Arnon Nagler, Eric R Lechman, John E Dick, Erno Wienholds, Shai Izraeli, Michael Milyavsky
Acute leukemia is an aggressive blood malignancy with low survival rates. A high expression of stem-like programs in leukemias predicts poor prognosis and is assumed to act in an aberrant fashion in the phenotypically heterogeneous leukemia stem cell (LSC) population. A lack of suitable genome engineering tools that can isolate LSCs based on their stemness precludes their comprehensive examination and full characterization. We hypothesized that tagging endogenous stemness-regulatory regions could generate a genome reporter for the putative leukemia stemness-state...
January 31, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30705410/mesenchymal-stem-cells-in-suppression-or-progression-of-hematologic-malignancy-current-status-and-challenges
#16
REVIEW
Myoung Woo Lee, Somi Ryu, Dae Seong Kim, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo
Mesenchymal stem cells (MSCs) are known for being multi-potent. However, they also possess anticancer properties, which has prompted efforts to adapt MSCs for anticancer therapies. However, MSCs have also been widely implicated in pathways that contribute to tumor growth. Numerous studies have been conducted to adapt MSCs for further clinical use; however, the results have been inconclusive, possibly due to the heterogeneity of MSC populations. Moreover, the conflicting roles of MSCs in tumor inhibition and tumor growth impede their adaptation for anticancer therapies...
January 31, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30700844/what-is-the-best-first-line-treatment-for-poems-syndrome-autologous-transplantation-melphalan-and-dexamethasone-or-lenalidomide-and-dexamethasone
#17
Hao Zhao, Xu-Fei Huang, Xue-Min Gao, Hao Cai, Lu Zhang, Jun Feng, Xin-Xin Cao, Dao-Bin Zhou, Jian Li
POEMS syndrome is a rare plasma cell dyscrasia. This study compared the responses to and survival of 347 POEMS syndrome patients given three first-line treatment regimens: autologous stem cell transplantation (ASCT, N = 165) and melphalan + dexamethasone (MDex, N = 79), or lenalidomide + dexamethasone (LDex, N = 103). After a median 45-month follow-up, overall hematologic complete remission (CRH ) was 46.4%, vascular endothelial growth factor complete remission (CRV ) was 55.1%, and neurological remission (RN ) was 93...
January 30, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30700843/telomere-length-predicts-for-outcome-to-fcr-chemotherapy-in-cll
#18
Kevin Norris, Peter Hillmen, Andrew Rawstron, Robert Hills, Duncan M Baird, Christopher D Fegan, Chris Pepper
We have previously shown that dividing patients with CLL into those with telomeres inside the fusogenic range (TL-IFR) and outside the fusogenic range (TL-OFR) is powerful prognostic tool. Here, we used a high-throughput version of the assay (HT-STELA) to establish whether telomere length could predict for outcome to fludarabine, cyclophosphamide, rituximab (FCR)-based treatment using samples collected from two concurrent phase II studies, ARCTIC and ADMIRE (n = 260). In univariate analysis, patients with TL-IFR had reduced progression-free survival (PFS) (P < 0...
January 30, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30700842/infections-associated-with-immunotherapeutic-and-molecular-targeted-agents-in-hematology-and-oncology-a-position-paper-by-the-european-conference-on-infections-in-leukemia-ecil
#19
REVIEW
Georg Maschmeyer, Julien De Greef, Sibylle C Mellinghoff, Annamaria Nosari, Anne Thiebaut-Bertrand, Anne Bergeron, Tomas Franquet, Nicole M A Blijlevens, Johan A Maertens
A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTOR inhibitors, ruxolitinib, and venetoclax, a detailed review of data available until August 2018 has been conducted, and specific recommendations for prophylaxis, diagnostic and differential diagnostic procedures as well as for clinical management have been developed...
January 30, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://read.qxmd.com/read/30700841/creating-novel-translation-inhibitors-to-target-pro-survival-proteins-in-chronic-lymphocytic-leukemia
#20
Rong Chen, Mingzhao Zhu, Rajan R Chaudhari, Omar Robles, Yuling Chen, Wesley Skillern, Qun Qin, William G Wierda, Shuxing Zhang, Kenneth G Hull, Daniel Romo, William Plunkett
The viability of chronic lymphocytic leukemia (CLL) is critically dependent upon staving off death by apoptosis, a hallmark of CLL pathophysiology. The recognition that Mcl-1, a major component of the anti-apoptotic response, is intrinsically short-lived and must be continually resynthesized suggested a novel therapeutic approach. Pateamine A (PatA), a macrolide marine natural product, inhibits cap-dependent translation by binding to the initiation factor eIF4A. In this study, we demonstrated that a synthetic derivative of PatA, des-methyl des-amino PatA (DMDAPatA), blocked mRNA translation, reduced Mcl-1 protein and initiated apoptosis in CLL cells...
January 30, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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