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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/29303505/generation-of-a-multi-antigen-directed-immune-response-for-durable-control-of-acute-lymphoblastic-leukemia
#1
S Jo, J H Lee, J J Mattei, D M Barrett, P van den Elzen, S A Grupp, G S D Reid, A E Seif
This corrects the article DOI: 10.1038/leu.2017.290.
January 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29271969/mir-194-5p-bclaf1-deregulation-in-aml-tumorigenesis
#2
C Dell'Aversana, C Giorgio, L D'Amato, G Lania, F Matarese, S Saeed, A Di Costanzo, V Belsito Petrizzi, C Ingenito, J H A Martens, I Pallavicini, S Minucci, A Carissimo, H G Stunnenberg, L Altucci
This corrects the article DOI: 10.1038/leu.2017.64.
December 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29257138/proteomic-analysis-of-jak2v617f-induced-changes-identifies-potential-new-combinatorial-therapeutic-approaches
#3
S Pearson, A J K Williamson, R Blance, T C P Somervaille, S Taylor, N Azadbakht, A D Whetton, A Pierce
This corrects the article DOI: 10.1038/leu.2017.143.
December 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29251284/prevention-and-management-of-adverse-events-of-novel-agents-in-multiple-myeloma-a-consensus-of-the-european-myeloma-network
#4
REVIEW
H Ludwig, M Delforge, T Facon, H Einsele, F Gay, P Moreau, H Avet-Loiseau, M Boccadoro, R Hajek, M Mohty, M Cavo, M A Dimopoulos, J F San-Miguel, E Terpos, S Zweegman, L Garderet, M-V Mateos, G Cook, X Leleu, H Goldschmidt, G Jackson, M Kaiser, K Weisel, N W C J van de Donk, A Waage, M Beksac, U H Mellqvist, M Engelhardt, J Caers, C Driessen, P Sonneveld
During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved 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 drugs 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...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29249823/flow-cytometric-vs-morphologic-assessment-of-remission-in-childhood-acute-lymphoblastic-leukemia-a-report-from-the-children-s-oncology-group-cog
#5
S Gupta, M Devidas, M L Loh, E A Raetz, S Chen, C Wang, P Brown, A J Carroll, N A Heerema, J M Gastier-Foster, K P Dunsmore, E C Larsen, K W Maloney, L A Mattano, S S Winter, N J Winick, W L Carroll, S P Hunger, M Borowitz, B L Wood
Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B- and T-precursor acute lymphoblastic leukemia (B-ALL, T-ALL). Although MRD determines depth of remission, remission remains defined by morphology. We determined the outcomes of children with discordant assessments of remission by morphology vs flow cytometry using patients aged 1-30.99 years enrolled on Children's Oncology Group ALL trials who underwent bone marrow assessment at the end of induction (N=9350). Morphologic response was assessed locally as M1 (<5% lymphoblasts; remission), M2 (5-25%) or M3 (>25%)...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29249822/phase-i-ii-trial-of-the-oral-regimen-ixazomib-pomalidomide-and-dexamethasone-in-relapsed-refractory-multiple-myeloma
#6
A Krishnan, P Kapoor, J M Palmer, N-C Tsai, S Kumar, S Lonial, M Htut, C Karanes, N Nathwani, M Rosenzweig, F Sahebi, G Somlo, L Duarte, J F Sanchez, D Auclair, S J Forman, J G Berdeja
In this phase I/II trial, a triplet regimen of ixazomib (Ixa: 3 or 4 mg), pomalidomide (Pom: 4 mg), and dexamethasone (Dex: 40 mg) was administered to 32 lenalidomide-refractory multiple myeloma (MM) patients; 31 were evaluable for response and toxicity. At dose level 1 (DL1, 3 mg Ixa), 1/3 patients experienced grade 3 fatigue, grade 3 lung infection, grade 4 neutropenia, and grade 4 thrombocytopenia; all were considered dose limiting. Per 3+3 phase I design, an additional 3 patients were enrolled to DL1, with no further dose limiting toxicity (DLT)...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29249821/aza-ms-a-novel-multiparameter-mass-spectrometry-method-to-determine-the-intracellular-dynamics-of-azacitidine-therapy-in-vivo
#7
A Unnikrishnan, A V N Quynh, R Pickford, M J Raftery, A C Nunez, A Verma, L B Hesson, J E Pimanda
The cytidine analogue, 5-azacytidine (AZA; 5-AZA-cR), is the primary treatment for myelodysplastic syndrome and chronic myelomonocytic leukaemia. However, only ~50% of treated patients will respond to AZA and the drivers of AZA resistance in vivo are poorly understood. To better understand the intracellular dynamics of AZA upon therapy and decipher the molecular basis for AZA resistance, we have developed a novel, multiparameter, quantitative mass spectrometry method (AZA-MS). Using AZA-MS, we have accurately quantified the abundance of the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA and the cytoplasm within the same sample using nanogram quantities of input material...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29249820/setd2-mediated-crosstalk-between-h3k36me3-and-h3k79me2-in-mll-rearranged-leukemia
#8
J Bu, A Chen, X Yan, F He, Y Dong, Y Zhou, J He, D Zhan, P Lin, Y Hayashi, Y Sun, Y Zhang, Z Xiao, H L Grimes, Q-F Wang, G Huang
Previously, we identified SETD2 loss-of-function mutations in 22% of MLL-rearranged (MLLr) acute leukemia patients, implicating a mechanism for cooperativity between SETD2 mutations and MLL fusions. However, the detailed mechanism of how SETD2-H3K36me3 downregulation accelerates MLLr leukemia remains unclear. Here, we show that in MLLr leukemia, both H3K79me2 and H3K36me3 are aberrantly elevated and co-enriched in a group of genes. SETD2 inactivation leads to a global reduction of H3K36me3 and a further elevation of H3K79me2, but does not change the expression of known MLL fusion target genes...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29249819/chromothripsis-in-acute-myeloid-leukemia-biological-features-and-impact-on-survival
#9
M C Fontana, G Marconi, J D M Feenstra, E Fonzi, C Papayannidis, A G L di Rorá, A Padella, V Solli, E Franchini, E Ottaviani, A Ferrari, C Baldazzi, N Testoni, I Iacobucci, S Soverini, T Haferlach, V Guadagnuolo, L Semerad, M Doubek, M Steurer, Z Racil, S Paolini, M Manfrini, M Cavo, G Simonetti, R Kralovics, G Martinelli
Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study define incidence of chromothripsis in 395 newly-diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix®) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (P=0...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29249818/persistence-of-pre-leukemic-clones-during-first-remission-and-risk-of-relapse-in-acute-myeloid-leukemia
#10
M Rothenberg-Thurley, S Amler, D Goerlich, T Köhnke, N P Konstandin, S Schneider, M C Sauerland, T Herold, M Hubmann, B Ksienzyk, E Zellmeier, S K Bohlander, M Subklewe, A Faldum, W Hiddemann, J Braess, K Spiekermann, K H Metzeler
Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance of these clones for AML relapse. Here, we characterized paired pre-treatment and remission samples from 126 AML patients for mutations in 68 leukemia-associated genes. Fifty patients (40%) retained ⩾1 mutation during remission at a variant allele frequency of ⩾2%...
December 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29229977/proteomic-and-genomic-integration-identifies-kinase-and-differentiation-determinants-of-kinase-inhibitor-sensitivity-in-leukemia-cells
#11
P Casado, E H Wilkes, F Miraki-Moud, M M Hadi, A Rio-Machin, V Rajeeve, R Pike, S Iqbal, S Marfa, N Lea, S Best, J Gribben, J Fitzgibbon, P R Cutillas
Leukemia accepted article preview online, 12 December 2017. doi:10.1038/leu.2017.349.
December 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29209044/biological-and-prognostic-impact-of-apobec-induced-mutations-in-the-spectrum-of-plasma-cell-dyscrasias-and-multiple-myeloma-cell-lines
#12
F Maura, M Petljak, M Lionetti, I Cifola, W Liang, E Pinatel, L Alexandrov, A Fullam, I Martincorena, K J Dawson, N Angelopoulos, M K Samur, R Szalat, J Zamora, P Tarpey, H Davies, P Corradini, K Anderson, S Minvielle, A Neri, H Avet-Loiseau, J J Keats, P J Campbell, N Munshi, N Bolli
Leukemia accepted article preview online, 06 December 2017. doi:10.1038/leu.2017.345.
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29209043/crispr-cas9-edited-nsg-mice-as-pdx-models-of-human-leukemia-to-address-the-role-of-niche-derived-sparc
#13
I Tirado-Gonzalez, E Czlonka, A Nevmerzhitskaya, D Soetopo, E Bergonzani, A Mahmoud, A Contreras, I Jeremias, U Platzbecker, J P Bourquin, U Kloz, F Van der Hoeven, H Medyouf
Leukemia accepted article preview online, 06 December 2017. doi:10.1038/leu.2017.346.
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29209042/analysis-of-the-genomic-landscape-of-multiple-myeloma-highlights-novel-prognostic-markers-and-disease-subgroups
#14
N Bolli, G Biancon, M Moarii, S Gimondi, Y Li, C de Philippis, F Maura, V Sathiaseelan, Y-T Tai, L Mudie, S O'Meara, K Raine, J W Teague, A P Butler, C Carniti, M Gerstung, T Bagratuni, E Kastritis, M Dimopoulos, P Corradini, K Anderson, P Moreau, S Minvielle, P J Campbell, E Papaemmanuil, H Avet-Loiseau, N 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 changes (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 IMiD-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene...
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29209041/the-e3-ubiquitin-ligase-wwp1-sustains-the-growth-of-acute-myeloid-leukaemiaag-sanarico-et-al
#15
A G Sanarico, C Ronchini, A Croce, E M Memmi, U A Cammarata, A De Antoni, S Lavorgna, M Divona, L Giacò, G E M Melloni, A Brendolan, G Simonetti, G Martinelli, P Mancuso, F Bertolini, F L Coco, G Melino, P G Pelicci, F Bernassola
The E3 ubiquitin ligase (E3) WWP1 is an oncogenic factor implicated in the maintenance of different types of epithelial cancers. The role of WWP1 in haematological neoplasms remains unknown. Acute myeloid leukaemia (AML) is characterized by the expansion of malignant myeloid cells blocked at different stages of differentiation. Here, we report that the expression of WWP1 is significantly augmented in a large cohort of primary AML patients and in AML cell lines, compared to hematopoietic cells from healthy donors...
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29203856/somatic-cll-mutations-occur-at-multiple-distinct-hematopoietic-maturation-stages-documentation-and-cautionary-note-regarding-cell-fraction-purity
#16
S Marsilio, H Khiabanian, G Fabbri, S Vergani, C Scuoppo, E Montserrat, E J Shpall, M Hadigol, P Marin, K R Rai, R Rabadan, S Devereux, L Pasqualucci, N Chiorazzi
Leukemia accepted article preview online, 05 December 2017. doi:10.1038/leu.2017.343.
December 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29249817/drug-induced-inhibition-of-phosphorylation-of-stat5-overrides-drug-resistance-in-neoplastic-mast-cells
#17
B Peter, S Bibi, G Eisenwort, B Wingelhofer, D Berger, G Stefanzl, K Blatt, H Herrmann, E Hadzijusufovic, G Hoermann, T Hoffmann, J Schwaab, M Jawhar, M Willmann, W R Sperr, J Zuber, K Sotlar, H-P Horny, R Moriggl, A Reiter, M Arock, P Valent
Systemic mastocytosis (SM) is a mast cell (MC) neoplasm with complex pathology and a variable clinical course. In aggressive SM (ASM) and MC leukemia (MCL), responses to conventional drugs are poor and the prognosis is dismal. R763 is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT and FLT3. We examined the effects of R763 on proliferation and survival of neoplastic MC. R763 produced dose-dependent inhibition of proliferation in the human MC lines HMC-1.1 (IC50 5-50 nM), HMC-1...
November 29, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29180669/myc-containing-amplicons-in-acute-myeloid-leukemia-genomic-structures-evolution-and-transcriptional-consequences
#18
A ĹAbbate, D Tolomeo, I Cifola, M Severgnini, A Turchiano, B Augello, G Squeo, P D Addabbo, D Traversa, G Daniele, A Lonoce, M Pafundi, M Carella, O Palumbo, A Dolnik, D Muehlematter, J Schoumans, N Van Roy, G De Bellis, G Martinelli, G Merla, L Bullinger, C Haferlach, C T Storlazzi
Double minutes (dmin), homogeneously staining regions, and ring chromosomes are vehicles of gene amplification in cancer. The underlying mechanism leading to their formation as well as their structure and function in acute myeloid leukemia (AML) remain mysterious. We combined a range of high-resolution genomic methods to investigate the architecture and expression pattern of amplicons involving chromosome band 8q24 in 23 cases of AML (AML-amp). This revealed that different MYC-dmin architectures can coexist within the same leukemic cell population, indicating a step-wise evolution rather than a single event origin, such as through chromothripsis...
November 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29160863/whole-genome-sequencing-of-chronic-lymphocytic-leukaemia-reveals-distinct-differences-in-the-mutational-landscape-between-ighv-mut-and-ighv-unmut-subgroups
#19
A Burns, R Alsolami, J Becq, B Stamatopoulos, A Timbs, D Bruce, P Robbe, D Vavoulis, R Clifford, M Cabes, H Dreau, J Taylor, S J L Knight, R Mansson, D Bentley, R Beekman, J I Martín-Subero, E Campo, R S Houlston, K E Ridout, A Schuh
This corrects the article DOI: 10.1038/leu.2017.177.
November 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29158558/protein-arginine-methyltransferase-5-prmt5-has-prognostic-relevance-and-is-a-druggable-target-in-multiple-myeloma
#20
A Gullà, T Hideshima, G Bianchi, M Fulciniti, M K Samur, J Qi, Y-T Tai, T Harada, E Morelli, N Amodio, R Carrasco, P Tagliaferri, N C Munshi, P Tassone, K C Anderson
Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased PFS and OS...
November 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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