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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/28210006/a-novel-lsd1-inhibitor-ncd38-ameliorates-mds-related-leukemia-with-complex-karyotype-by-attenuating-leukemia-programs-via-activating-super-enhancers
#1
N Sugino, M Kawahara, G Tatsumi, A Kanai, H Matsui, R Yamamoto, Y Nagai, S Fujii, Y Shimazu, M Hishizawa, T Inaba, A Andoh, T Suzuki, A Takaori-Kondo
Lysine-specific demethylase 1 (LSD1) regulates gene expression by affecting histone modifications and is a promising target for acute myeloid leukemia (AML) with specific genetic abnormalities. Novel LSD1 inhibitors, NCD25 and NCD38, inhibited growth of MLL-AF9 leukemia as well as erythroleukemia, megakaryoblastic leukemia and myelodysplastic syndromes (MDS) overt leukemia cells in the concentration range that normal hematopoiesis was spared. NCD25 and NCD38 invoked the myeloid development programs, hindered the MDS and AML oncogenic programs, and commonly upregulated 62 genes in several leukemia cells...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28210005/mll-is-essential-for-nup98-hoxa9-induced-leukemia
#2
Y Shima, M Yumoto, T Katsumoto, I Kitabayashi
Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with MLL via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28210004/monoclonal-antibody-therapy-in-multiple-myeloma
#3
REVIEW
Cyrille Touzeau, Philippe Moreau, Charles Dumontet
The therapeutic landscape of multiple myeloma (MM) has evolved spectacularly over the past decade with the discovery and validation of proteasome inhibitors and immunomodulatory agents as highly active agents, both in front-line therapy as well as in the relapse and maintenance settings. While previous attempts to apply available monoclonal antibodies (Mabs) to the treatment of patients with MM has until recently been disappointing, novel targets specifically explored in the context of MM have recently lead to the first approvals of Mabs for the treatment of patients with MM...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28210003/differential-signaling-through-p190-and-p210-bcr-abl-fusion-proteins-revealed-by-interactome-and-phosphoproteome-analysis
#4
J A Cutler, R Tahir, S K Sreenivasamurthy, C Mitchell, S Renuse, R S Nirujogi, A H Patil, M Heydarian, X Wong, X Wu, T-C Huang, M-S Kim, K Reddy, A Pandey
Two major types of leukemogenic BCR-ABL fusion proteins are p190(BCR-ABL) and p210(BCR-ABL). Although the two fusion proteins are closely related, they can lead to different clinical outcomes. A thorough understanding of the signaling programs employed by these two fusion proteins is necessary to explain these clinical differences. We took an integrated approach by coupling protein-protein interaction analysis using biotinylation identification (BioID) with global phosphorylation analysis to investigate the differences in signaling between these two fusion proteins...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28210002/analytical-and-clinical-validation-of-a-novel-in-house-deep-sequencing-method-for-minimal-residual-disease-monitoring-in-a-phase-ii-trial-for-multiple-myeloma
#5
J Martinez-Lopez, B Sanchez-Vega, S Barrio, I Cuenca, Y Ruiz-Heredia, R Alonso, I Rapado, C Marin, M-T Cedena, B Paiva, N Puig, M-V Mateos, R Ayala, M-T Hernández, C Jimenez, L Rosiñol, R Martínez, A-I Teruel, N Gutiérrez, M-L Martin-Ramos, A Oriol, J Bargay, J Bladé, J San-Miguel, R Garcia-Sanz, J-J Lahuerta
Leukemia accepted article preview online, 17 February 2017. doi:10.1038/leu.2017.58.
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28202953/fully-human-cd19-specific-chimeric-antigen-receptors-for-t-cell-therapy
#6
D Sommermeyer, T Hill, S M Shamah, A I Salter, Y Chen, K M Mohler, S R Riddell
Impressive results have been achieved by adoptively transferring T-cells expressing CD19-specific CARs with binding domains from murine mAbs to treat B-cell malignancies. T-cell mediated immune responses specific for peptides from the murine scFv antigen-binding domain of the CAR can develop in patients and result in premature elimination of CAR-T-cells increasing the risk of tumor relapse. As fully human scFv might reduce immunogenicity, we generated CD19-specific human scFvs with similar binding characteristics as the murine FMC63-derived scFv using human Ab/DNA-libraries...
February 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28196984/letter-to-the-editor-cbf%C3%AE-smmhc-regulates-ribosomal-gene-transcription-and-alters-ribosome-biogenesis
#7
G Cordonnier, A Mandoli, A Radhouane, G Hypolite, L Lhermitte, M Belhocine, V Asnafi, E Macintyre, J H A Martens, S Fumagalli, J Bond
Leukemia accepted article preview online, 15 February 2017. doi:10.1038/leu.2017.53.
February 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28196983/genomic-profiling-of-acute-lymphoblastic-leukemia-in-ataxia-telangiectasia-patients-reveals-tight-link-between-atm-mutations-and-chromothripsis
#8
M Ratnaparkhe, M Hlevnjak, T Kolb, A Jauch, K K Maass, F Devens, A Rode, V Hovestadt, A Korshunov, A Pastorczak, W Mlynarski, S Sungalee, J Korbel, J Hoell, U Fischer, T Milde, C Kramm, M Nathrath, K Chrzanowska, E Tausch, M Takagi, T Taga, S Constantini, J Loeffen, J Meijerink, S Zielen, G Gohring, B Schlegelberger, E Maass, R Siebert, J Kunz, A E Kulozik, B Worst, D T Jones, S M Pfister, M Zapatka, P Lichter, A Ernst
Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair...
February 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28194039/donor-cell-leukemia-arising-from-preleukemic-clones-with-a-novel-germline-ddx41-mutation-after-allogenic-hematopoietic-stem-cell-transplantation
#9
S Kobayashi, A Kobayashi, Y Osawa, S Nagao, K Takano, Y Okada, N Tachi, M Teramoto, T Kawamura, T Horiuchi, S Kato, T Maekawa, T Yamamura, J Watanabe, Y Harada, H Harada, K Sato, F Kimura
No abstract text is available yet for this article.
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28194038/itd-mutation-in-flt3-tyrosine-kinase-promotes-warburg-effect-and-renders-therapeutic-sensitivity-to-glycolytic-inhibition
#10
H-Q Ju, G Zhan, A Huang, Y Sun, S Wen, J Yang, W-H Lu, R-H Xu, J Li, Y Li, G Garcia-Manero, P Huang, Y Hu
Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28193998/inhibition-of-serotonin-receptor-type-1-in-acute-myeloid-leukemia-impairs-leukemia-stem-cell-functionality-a-promising-novel-therapeutic-target
#11
A Etxabe, M C Lara-Castillo, J M Cornet-Masana, A Banús-Mulet, M Nomdedeu, M A Torrente, M Pratcorona, M Díaz-Beyá, J Esteve, R M Risueño
Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous neoplasia with poor outcome, organized as a hierarchy initiated and maintained by a subpopulation with differentiation and self-renewal capacities called leukemia stem cells (LSCs). Although currently used chemotherapy is capable of initially reducing the tumor burden producing a complete remission, most patients will ultimately relapse and will succumb to their disease. As such, new therapeutic strategies are needed. AML cells differentially expressed serotonin receptors type 1 (HTR1) compared to healthy blood cells and the most primitive hematopoietic fraction; in fact, HTR1B expression on AML patient samples correlated with clinical outcome...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28111466/bortezomib-and-thalidomide-maintenance-after-stem-cell-transplantation-for-multiple-myeloma-a-pethema-gem-trial
#12
L Rosiñol, A Oriol, A I Teruel, A L de la Guía, MaJ Blanchard, J de la Rubia, M Granell, MaA Sampol, L Palomera, Y González, MaA Etxebeste, R Martínez-Martínez, M T Hernández, F de Arriba, A Alegre, MaT Cibeira, MaV Mateos, J Martínez-López, J J Lahuerta, J San Miguel, J Bladé
The phase III trial GEM05MENOS65 randomized 390 patients 65 years old or younger with newly diagnosed symptomatic multiple myeloma (MM) to receive induction with thalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone and Vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone bortezomib (VBMCP/VBAD/B) followed by autologous stem cell transplantation (ASCT) with MEL-200. After ASCT, a second randomization was performed to compare thalidomide/bortezomib (TV), thalidomide (T) and alfa-2b interferon (alfa2-IFN)...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28111464/bruton-s-tyrosine-kinase-inhibition-increases-bcl-2-dependence-and-enhances-sensitivity-to-venetoclax-in-chronic-lymphocytic-leukemia
#13
J Deng, E Isik, S M Fernandes, J R Brown, A Letai, M S Davids
Although the BTK inhibitor ibrutinib has transformed the management of patients with chronic lymphocytic leukemia (CLL), it does not induce substantial apoptosis in vitro, and as such the mechanisms underlying its ability to kill CLL cells are not well understood. Acalabrutinib, a more specific BTK inhibitor now in development, also appears to be highly effective in CLL, but the connection of its mechanism with CLL cell death is also unclear. Using dynamic BH3 profiling, we analyzed alterations in the function of the mitochondrial apoptotic pathway induced by ibrutinib and acalabrutinib...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28111462/biological-and-clinical-consequences-of-npm1-mutations-in-aml
#14
REVIEW
E M Heath, S M Chan, M D Minden, T Murphy, L I Shlush, A D Schimmer
Acute myeloid leukemia (AML) is characterized by accumulation of myeloid cells in the bone marrow because of impaired differentiation and proliferation, resulting in hematopoietic insufficiency. NPM1 is one of the most commonly mutated genes in AML, present in 20-30% of cases. Mutations in NPM1 represent a distinct entity in the World Health Organization (WHO) classification and commonly indicate a better risk prognosis. In this review, we discuss the many functions of NPM1, the consequence of mutations in NPM1 and possible mechanisms through which mutations lead to leukemogenesis...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28186131/recq1-helicase-is-involved-in-replication-stress-survival-and-drug-resistance-in-multiple-myeloma
#15
E Viziteu, B Klein, J Basbous, Y-L Lin, C Hirtz, C Gourzones, L Tiers, A Bruyer, L Vincent, C Grandmougin, A Seckinger, H Goldschmidt, A Constantinou, P Pasero, D Hose, J Moreaux
Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here, we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28138160/impact-of-salvage-regimens-on-response-and-overall-survival-in-acute-myeloid-leukemia-with-induction-failure
#16
M Wattad, D Weber, K Döhner, J Krauter, V I Gaidzik, P Paschka, M Heuser, F Thol, T Kindler, M Lübbert, H R Salih, A Kündgen, H-A Horst, P Brossart, K Götze, D Nachbaur, C-H Köhne, M Ringhoffer, G Wulf, G Held, H Salwender, A Benner, A Ganser, H Döhner, R F Schlenk
We evaluated the impact of salvage regimens and allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) with induction failure. Between 1993 and 2009, 3324 patients with newly diagnosed AML were enrolled in 5 prospective treatment trials of the German-Austrian AML Study Group. After first induction therapy with idarubicin, cytarabine and etoposide (ICE), 845 patients had refractory disease. In addition, 180 patients, although responding to first induction, relapsed after second induction therapy...
February 10, 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
#17
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...
February 10, 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
#18
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, 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. 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...
February 10, 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
#19
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
No abstract text is available yet for this article.
February 10, 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
#20
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, E L 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)...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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