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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/28331227/zdhhc11-and-zdhhc11b-are-critical-novel-components-of-the-oncogenic-myc-mir-150-myb-network-in-burkitt-lymphoma
#1
A Dzikiewicz-Krawczyk, K Kok, I Slezak-Prochazka, J-L Robertus, J Bruining, M M Tayari, B Rutgers, D de Jong, J Koerts, A Seitz, J Li, B Tillema, J E Guikema, I M Nolte, A Diepstra, L Visser, J Kluiver, A van den Berg
Leukemia accepted article preview online, 23 March 2017. doi:10.1038/leu.2017.94.
March 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28331226/the-histone-deacetylase-inhibitor-givinostat-itf2357-exhibits-potent-anti-tumor-activity-against-crlf2-rearranged-bcp-all
#2
A M Savino, J Sarno, L Trentin, M Vieri, G Fazio, M Bardini, C Bugarin, G Fossati, K Davis, G Gaipa, S Izraeli, L H Meyer, G P Nolan, A Biondi, G Te Kronnie, C Palmi, G Cazzaniga
Leukemias bearing CRLF2 and JAK2 gene alterations are characterized by aberrant JAK/STAT signaling and poor prognosis. The HDAC inhibitor givinostat/ITF2357 has been shown to exert antineoplastic activity against both systemic juvenile idiopathic arthritis and myeloproliferative neoplasms through inhibition of the JAK/STAT pathway. These findings led us to hypothesize that givinostat might also act against CRLF2-rearranged BCP-ALL, which lack effective therapies. Here, we found that givinostat inhibited proliferation and induced apoptosis of BCP-ALL CRLF2-rearranged cell lines, positive for exon 16 JAK2 mutations...
March 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28322237/characteristics-and-outcome-of-patients-with-therapy-related-acute-promyelocytic-leukemia-front-line-treated-with-or-without-arsenic-trioxide
#3
S Kayser, J Krzykalla, M A Elliott, K Norsworthy, P Gonzales, R K Hills, M R Baer, Z Ráčil, J Mayer, J Novak, P Žák, T Szotkowski, D Grimwade, N H Russell, R B Walter, E H Estey, J Westermann, M Görner, A Benner, A Krämer, B D Smith, A K Burnett, C Thiede, C Röllig, A D Ho, G Ehninger, R F Schlenk, M S Tallman, M J Levis, U Platzbecker
Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA, and 5% for CTX/ATO/ATRA...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28322226/highly-effective-combination-of-lsd1-kdm1a-antagonist-and-pan-histone-deacetylase-inhibitor-against-human-aml-cells
#4
W Fiskus, S Sharma, B Shah, B P Portier, S G T Devaraj, K Liu, S P Iyer, D Bearss, K N Bhalla
No abstract text is available yet for this article.
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28321124/combined-inhibition-of-%C3%AE-catenin-and-bcr-abl-synergistically-targets-tyrosine-kinase-inhibitor-resistant-blast-crisis-chronic-myeloid-leukemia-blasts-and-progenitors-in-vitro-and-in-vivo
#5
H Zhou, P Y Mak, H Mu, D H Mak, Z Zeng, J Cortes, Q Liu, M Andreeff, B Z Carter
Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent β-catenin activation remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of β-catenin in BC-CML stem/progenitor cells, particularly in GMP progenitors, and highest among a novel CD34(+)CD38(+)CD123(hi)Tim-3(hi) subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of β-catenin and its target CD44 in CML cells...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28321123/the-mutational-oncoprint-of-recurrent-cytogenetic-abnormalities-in-adult-patients-with-de-novo-acute-myeloid-leukemia
#6
A-K Eisfeld, K Mrózek, J Kohlschmidt, D Nicolet, S Orwick, C J Walker, K W Kroll, J S Blachly, A J Carroll, J E Kolitz, B L Powell, E S Wang, R M Stone, A de la Chapelle, J C Byrd, C D Bloomfield
Recurrent chromosomal abnormalities and gene mutations detected at the time of diagnosis of acute myeloid leukemia (AML) are associated with particular disease features, treatment response and survival of AML patients, and are used to denote specific disease entities in the World Health Organization classification of myeloid neoplasms and acute leukemia. However, large studies that integrate cytogenetic and comprehensive mutational information are scarce. We created a comprehensive oncoprint of mutations associated with recurrent cytogenetic findings by combining the information on mutational patterns of 80 cancer- and leukemia-associated genes with cytogenetic findings in 1603 adult patients with de novo AML...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28321122/the-emerging-roles-of-tumor-derived-exosomes-in-hematological-malignancies
#7
REVIEW
M Boyiadzis, T L Whiteside
Exosomes are small (30-150 nm) membranous vesicles of endocytic origin produced by all cells under physiological and pathological conditions. They have recently emerged as vehicles for intercellular transfer of molecular and genetic contents from parent to recipient cells. Exosome-mediated transfer of proteins or genes (RNA, miRNA, DNA) results in reprogramming of recipient cell functions. Exosomes carry and deliver information that is essential for health, and they participate in pathological events, including malignant transformation...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28321121/dnmt3a-regulates-t-cell-development-and-suppresses-t-all-transformation
#8
A C Kramer, A Kothari, W C Wilson, H Celik, J Nikitas, C Mallaney, E L Ostrander, E Eultgen, A Martens, M C Valentine, A L Young, T E Druley, M E Figueroa, B Zhang, G A Challen
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm resulting from the malignant transformation of T-cell progenitors, and comprises approximately 15 and 25% of pediatric and adult ALL cases respectively. It is well-established that activating NOTCH1 mutations are the major genetic lesions driving T-ALL in most patients, but efforts to develop targeted therapies against this pathway have produced limited success in decreasing leukemic burden and come with significant clinical side effects...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28321120/decision-analysis-of-allogeneic-hematopoietic-stem-cell-transplantation-for-patients-with-myelodysplastic-syndrome-stratified-according-to-the-revised-international-prognostic-scoring-system-ipss-r
#9
M G Della Porta, C H Jackson, E P Alessandrino, M Rossi, A Bacigalupo, M T van Lint, M Bernardi, B Allione, A Bosi, S Guidi, V Santini, L Malcovati, M Ubezio, C Milanesi, E Todisco, M T Voso, P Musto, F Onida, A P Iori, R Cerretti, G Grillo, A Molteni, P Pioltelli, L Borin, E Angelucci, E Oldani, S Sica, C Pascutto, V Ferretti, A Santoro, F Bonifazi, M Cazzola, A Rambaldi
Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R)...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28321119/notch1-mutated-chronic-lymphocytic-leukemia-cells-are-characterized-by-a-myc-related-overexpression-of-nucleophosmin-1-and-ribosome-associated-components
#10
F Pozzo, T Bittolo, E Vendramini, R Bomben, P Bulian, F M Rossi, A Zucchetto, E Tissino, M Degan, G D'Arena, F Di Raimondo, F Zaja, G Pozzato, D Rossi, G Gaidano, G Del Poeta, V Gattei, M Dal Bo
In chronic lymphocytic leukemia (CLL), the mechanisms controlling cell growth and proliferation in presence of NOTCH1 mutations remain largely unexplored. By performing a gene expression profile of NOTCH1 mutated (NOTCH1-mut) versus NOTCH1 wild type CLL, we identified a gene signature of NOTCH1-mut CLL characterized by upregulation of genes related to ribosome biogenesis, such as nucleophosmin1 (NPM1) and ribosomal proteins (RNPs). Activation of NOTCH1 signaling by EDTA or by co-culture with JAGGED1-expressing stromal cells increased NPM1 expression, and inhibition of NOTCH1 signaling by either NOTCH1-specific small interfering RNA (siRNA) or γ-secretase inhibitor reduced NPM1 expression...
March 21, 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
#11
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...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28303892/how-good-are-we-at-predicting-the-fate-of-someone-with-acute-myeloid-leukaemia
#12
EDITORIAL
E Estey, R P Gale
No abstract text is available yet for this article.
March 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28293022/response-adapted-consolidation-with-bortezomib-after-asct-improves-progression-free-survival-in-newly-diagnosed-multiple-myeloma
#13
H Einsele, S Knop, M Vogel, J Müller, M Kropff, B Metzner, C Langer, H Sayer, W Jung, H A Dürk, H Salwender, H Wandt, F Bassermann, M Gramatzki, W Rösler, H-H Wolf, W Brugger, M Engelhardt, T Fischer, P Liebisch, C Straka
Leukemia accepted article preview online, 15 March 2017. doi:10.1038/leu.2017.83.
March 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28232744/the-t-all-related-gene-bcl11b-regulates-the-initial-stages-of-human-t-cell-differentiation
#14
V L Ha, A Luong, F Li, D Casero, J Malvar, Y M Kim, R Bhatia, G M Crooks, C Parekh
The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies, we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials, and the induction of T-lineage genes, during the initial stages of human T-cell differentiation...
March 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28232743/cobll1-is-linked-to-drug-resistance-and-blastic-transformation-in-chronic-myeloid-leukemia
#15
S H Han, S-H Kim, H-J Kim, Y Lee, S-Y Choi, G Park, D-H Kim, A Lee, J Kim, J-M Choi, Y Kim, K Myung, H Kim, D-W Kim
Drug resistance to BCR-ABL1 tyrosine kinase inhibitor (TKI) and disease progression to blast crisis (BC) are major clinical problems in chronic myeloid leukemia (CML); however, underlying mechanisms governing this process remain to be elucidated. Here, we report Cordon-bleu protein-like 1 (Cobll1) as a distinct molecular marker associated with drug resistance as well as progression to BC. In detail, Cobll1 increases IKKγ stability, leading to NF-κB activation and reduction of nilotinib-dependent apoptosis, suggesting Cobll1-mediated NF-κB could be involved in drug resistance...
March 14, 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
#16
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...
March 14, 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
#17
REVIEW
C Touzeau, P Moreau, C 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. Although 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...
March 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28167833/validation-of-risk-stratification-models-in-acute-myeloid-leukemia-using-sequencing-based-molecular-profiling
#18
M Wang, J Lindberg, D Klevebring, C Nilsson, A S Mer, M Rantalainen, S Lehmann, H Grönberg
Risk stratification of acute myeloid leukemia (AML) patients needs improvement. Several AML risk classification models based on somatic mutations or gene-expression profiling have been proposed. However, systematic and independent validation of these models is required for future clinical implementation. We performed whole-transcriptome RNA-sequencing and panel-based deep DNA sequencing of 23 genes in 274 intensively treated AML patients (Clinseq-AML). We also utilized the The Cancer Genome Atlas (TCGA)-AML study (N=142) as a second validation cohort...
March 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28270692/imetelstat-a-telomerase-inhibitor-differentially-affects-normal-and-malignant-megakaryopoiesis
#19
G Mosoyan, T Kraus, F Ye, K Eng, J D Crispino, R Hoffman, C Iancu-Rubin
Imetelstat (GRN163L) is a specific telomerase inhibitor which has demonstrated clinical activity in patients with myeloproliferative neoplasms (MPN) and in patients with solid tumors. The antitumor effects were associated with the development of thrombocytopenia, one of the common side effects observed in patients treated with imetelstat. The events underlying these adverse effects are not apparent. In this report we investigated the potential mechanisms that account for imetelstat's beneficial effects in MPN patients and the manner by which imetelstat treatment leads to a reduction in platelet numbers...
March 8, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28270691/alloreactivity-the-janus-face-of-hematopoietic-stem-cell-transplantation
#20
A Gratwohl, A Sureda, J Cornelissen, J Apperley, P Dreger, R Duarte, H T Greinix, E Mc Grath, N Kroeger, F Lanza, A Nagler, J A Snowden, D Niederwieser, R Brand
Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, whilst preserving antitumor alloreactivity...
March 8, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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