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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/28100909/impact-of-pretransplant-induction-therapy-on-autologous-stem-cell-transplantation-for-patients-with-newly-diagnosed-poems-syndrome
#1
J Li, M-H Duan, C Wang, X-F Huang, W Zhang, X-X Cao, T-N Zhu, J-L Zhuang, B Han, H Cai, H-C Cai, D-B Zhou
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, Monoclonal gammopathy and skin changes) is a rare plasma cell dyscrasia sometimes treated with a haematopoietic cell autotransplant. We analyzed data from 138 subjects with newly-diagnosed POEMS syndrome receiving a autotransplant at our centre. Thirty-two subjects with severe end-organ dysfunction ineligible for immediate autotransplant received pretransplant therapy which made a subsequent autotransplant feasible. Pretransplant therapy resulted in vascular endothelial growth factor (VEGF) remissions in 15 (47%)...
January 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28096537/jak2-v617f-activates-%C3%AE-1-integrin-mediated-adhesion-of-granulocytes-to-vascular-cell-adhesion-molecule-1-vcam1
#2
N Gupta, B Edelmann, T M Schnoeder, F C Saalfeld, D Wolleschak, S Kliche, B Schraven, F H Heidel, T Fischer
Leukemia accepted article preview online, 18 January 2017. doi:10.1038/leu.2017.26.
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28096536/germline-ikaros-mutation-associated-with-primary-immunodeficiency-that-progressed-to-t-cell-acute-lymphoblastic-leukemia
#3
N Yoshida, H Sakaguchi, H Muramatsu, Y Okuno, C Song, S Dovat, A Shimada, M Ozeki, H Ohnishi, T Teramoto, T Fukao, N Kondo, Y Takahashi, K Matsumoto, K Kato, S Kojima
Leukemia accepted article preview online, 18 January 2017. doi:10.1038/leu.2017.25.
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28096535/genetics-of-ancestry-specific-risk-for-relapse-in-acute-lymphoblastic-leukemia
#4
S E Karol, E Larsen, C Cheng, X Cao, W Yang, L B Ramsey, C A Fernandez, J R McCorkle, S W Paugh, R J Autry, E Lopez-Lopez, B Diouf, S Jeha, C-H Pui, E A Raetz, N J Winick, W L Carroll, S P Hunger, M L Loh, M Devidas, W E Evans, J J Yang, M V Relling
The causes of individual relapses in children with acute lymphoblastic leukemia (ALL) remain incompletely understood. We evaluated the contribution of germline genetic factors to relapse in 2225 children treated on Children's Oncology Group trial AALL0232. We identified 302 germline single nucleotide polymorphisms (SNPs) associated with relapse after adjusting for treatment and ancestry and 715 additional SNPs associated with relapse in an ancestry-specific manner. We tested for replication of these relapse-associated SNPs in external data sets of antileukemic drug pharmacokinetics and pharmacodynamics and an independent clinical cohort...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#5
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28096533/impact-of-pretreatment-characteristics-and-salvage-strategy-on-outcome-in-patients-with-relapsed-acute-myeloid-leukemia
#6
R F Schlenk, P Frech, D Weber, P Brossart, H-A Horst, D Kraemer, G Held, M Ringhoffer, A Burchardt, G Kobbe, K Götze, D Nachbaur, T Fischer, M Lübbert, H R Salih, H Salwender, G Wulf, E Koller, M Wattad, W Fiedler, S Kremers, H Kirchen, B Hertenstein, P Paschka, V I Gaidzik, V Teleanu, M Heuser, F Thol, K Döhner, J Krauter, A Ganser, H Döhner
Leukemia accepted article preview online, 18 January 2017. doi:10.1038/leu.2017.22.
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28093565/treatment-free-remission-in-chronic-myeloid-leukemia-floating-between-expectation-and-evidence
#7
M Baccarani
Leukemia accepted article preview online, 17 January 2017. doi:10.1038/leu.2017.20.
January 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28090092/the-clonal-origins-of-leukemic-progression-of-myelodysplasia
#8
T H Kim, M S Tyndel, H J Kim, J-S Ahn, S H Choi, H J Park, Y-K Kim, D-H Yang, J-J Lee, S-H Jung, S Y Kim, Y H Min, J-W Cheong, S K Sohn, J H Moon, M Choi, M Lee, Z Zhang, D Dong Hwan Kim
The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of 8 commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events...
January 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28090091/proposed-diagnostic-criteria-and-classification-of-basophilic-leukemias-and-related-disorders
#9
REVIEW
P Valent, K Sotlar, K Blatt, K Hartmann, A Reiter, I Sadovnik, W R Sperr, P Bettelheim, C Akin, K Bauer, T I George, E Hadzijusufovic, D Wolf, J Gotlib, F-X Mahon, D D Metcalfe, H-P Horny, M Arock
Basophils form a distinct cell lineage within the hematopoietic cell family. In various myeloid neoplasms, including chronic myeloid leukemia (CML), basophilia is frequently seen. Acute and chronic basophilic leukemias, albeit rare, have also been described. However, no generally accepted criteria and classification of basophilic leukemias have been presented to date. In order to address this unmet need, a series of Working Conferences and other meetings were organized between March 2015 and March 2016. The current article provides a summary of consensus statements from these meetings, together with proposed criteria to delineate acute basophilic leukemia (ABL) from chronic basophilic leukemia (CBL) and primary forms of the disease where no preceding myeloid malignancy is detected, from the more common ´secondary´ variants...
January 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28090090/incidence-and-prognostic-impact-of-asxl2-mutations-in-adult-acute-myeloid-leukemia-patients-with-t-8-21-q22-q22-a-study-of-the-german-austrian-aml-study-group-amlsg
#10
N Jahn, M Agrawal, L Bullinger, D Weber, A Corbacioglu, V I Gaidzik, L Schmalbrock, F Thol, M Heuser, J Krauter, G Göhring, A Kündgen, W Fiedler, M Wattad, G Held, C-H Köhne, H-A Horst, M Lübbert, A Ganser, R F Schlenk, H Döhner, K Döhner, P Paschka
Leukemia accepted article preview online, 16 January 2017. doi:10.1038/leu.2017.18.
January 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28090089/transfer-of-minimally-manipulated-cmv-specific-t-cells-from-stem-cell-or-third-party-donors-to-treat-cmv-infection-after-allohsct
#11
M Neuenhahn, J Albrecht, M Odendahl, F Schlott, G Dössinger, M Schiemann, S Lakshmipathi, K Martin, D Bunjes, S Harsdorf, E M Weissinger, H Menzel, M Verbeek, L Uharek, N Kröger, E Wagner, G Kobbe, T Schroeder, M Schmitt, G Held, W Herr, L Germeroth, H Bonig, T Tonn, H Einsele, D H Busch, G U Grigoleit
Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drug-refractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo MHC-Streptamer-isolated CMV epitope-specific donor T cells...
January 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28082737/phosphoproteomic-analysis-reveals-hyperactivation-of-mtor-stat3-and-lck-calcineurin-axes-in-pediatric-early-t-cell-precursor-all
#12
V Serafin, V Lissandron, B Buldini, S Bresolin, M Paganin, F Grillo, N Andriano, C Palmi, G Cazzaniga, S Marmiroli, V Conter, G Basso, B Accordi
Leukemia accepted article preview online, 13 January 2017. doi:10.1038/leu.2017.13.
January 13, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074072/targeting-bet-proteins-improves-the-therapeutic-efficacy-of-bcl-2-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#13
S Peirs, V Frismantas, F Matthijssens, W Van Loocke, T Pieters, N Vandamme, B Lintermans, M P Dobay, G Berx, B Poppe, S Goossens, B C Bornhauser, J-P Bourquin, P Van Vlierberghe
Inhibition of anti-apoptotic BCL-2 has recently emerged as a promising new therapeutic strategy for the treatment of a variety of human cancers, including leukemia. Here, we used T-cell acute lymphoblastic leukemia as a model system to identify novel synergistic drug combinations with the BH3 mimetic venetoclax (ABT-199). In vitro drug screening in primary leukemia specimens that were derived from patients with high risk of relapse or relapse and cell lines revealed synergistic activity between venetoclax and the BET bromodomain inhibitor JQ1...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074071/olaptesed-pegol-an-anti-cxcl12-sdf-1-spiegelmer-%C3%A2-alone-and-with-bortezomib-dexamethasone-in-relapsed-refractory-multiple-myeloma-a-phase-iia-study
#14
H Ludwig, K Weisel, M T Petrucci, X Leleu, A M Cafro, L Garderet, C Leitgeb, R Foa, R Greil, I Yakoub-Agha, D Zboralski, S Vauléon, T Dümmler, D Beyer, Ana Kruschinski, K Riecke, M Baumann, M Engelhardt
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.5.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074070/gain-of-function-in-jak2-v617f-positive-t-cells
#15
G Nishanth, D Wolleschak, C Fahldieck, T Fischer, A Mullally, F Perner, T M Schnöder, S Just, F H Heidel, D Schlüter
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.6.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074069/myelodysplastic-syndromes-and-bone-loss-in-mice-and-men
#16
H Weidner, M Rauner, F Trautmann, J Schmitt, E Balaian, A Mies, S Helas, U Baschant, C Khandanpour, M Bornhäuser, L C Hofbauer, U Platzbecker
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.7.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074068/a-cpg-island-methylator-phenotype-in-acute-myeloid-leukemia-independent-of-idh-mutations-and-associated-with-a-favorable-outcome
#17
A D Kelly, H Kroeger, J Yamazaki, R Taby, F Neumann, S Yu, J T Lee, B Patel, Y Li, R He, S Liang, Y Lu, M Cesaroni, S A Pierce, S M Kornblau, C E Bueso-Ramos, F Ravandi, H M Kantarjian, J Jelinek, J-Pj Issa
Genetic changes are infrequent in acute myeloid leukemia (AML) compared to other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation (DREAM) data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CIMP (A-CIMP(+))...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074067/expression-of-the-ctla-4-ligand-cd86-on-plasmacytoid-dendritic-cells-pdc-predicts-risk-of-disease-recurrence-after-treatment-discontinuation-in-cml
#18
C Schütz, S Inselmann, S Sausslele, C T Dietz, M C Müller, E Eigendorff, C A Brendel, S K Metzelder, T H Brümmendorf, C Waller, J Dengler, M E Goebeler, R Herbst, G Freunek, S Hanzel, T Illmer, Y Wang, T Lange, F Finkernagel, R Hehlmann, M Huber, A Neubauer, A Hochhaus, J Guilhot, F X Mahon, M Pfirrmann, A Burchert
It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86(+)pDC frequencies than normal donors (P<0·0024), whereas TFR patients had consistently low CD86(+)pDC (n=12)...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074066/preclinical-targeting-of-aggressive-t-cell-malignancies-using-anti-cd5-chimeric-antigen-receptor
#19
K H Chen, M Wada, K G Pinz, H Liu, K-W Lin, A Jares, A E Firor, X Shuai, H Salman, M Golightly, F Lan, L Senzel, L-H Leung, X Jiang, Y Ma
The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T cell acute lymphoblastic leukemia (T-ALL) and peripheral T cell lymphomas (PTCLs)...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074065/hdac3-activity-is-required-for-initiation-of-leukemogenesis-in-acute-promyelocytic-leukemia
#20
P Mehdipour, F Santoro, O A Botrugno, M Romanenghi, C Pagliuca, G M Matthews, R W Johnstone, S Minucci
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.3.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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