The Experts below are selected from a list of 58635 Experts worldwide ranked by ideXlab platform
Michael A Caligiuri - One of the best experts on this subject based on the ideXlab platform.
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targeting flt3 by chimeric antigen receptor t cells for the treatment of Acute Myeloid Leukemia
Leukemia, 2017Co-Authors: Liguang Chen, Hsiaoyin Mao, Jianying Zhang, Jianhong Chu, Steven M Devine, Michael A CaligiuriAbstract:Targeting FLT3 by chimeric antigen receptor T cells for the treatment of Acute Myeloid Leukemia
Miguel Munoz - One of the best experts on this subject based on the ideXlab platform.
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Human Acute Myeloid Leukemia cells express Neurokinin-1 receptor, which is involved in the antileukemic effect of Neurokinin-1 receptor antagonists
Investigational New Drugs, 2019Co-Authors: A. Molinos-quintana, P. Trujillo-hacha, J. I. Piruat, J. A. Bejarano-garcía, E. García-guerrero, José A. Pérez-simón, Miguel MunozAbstract:The substance P/neurokinin-1 receptor system has been implicated in tumor cell proliferation. Neurokinin-1 receptor has been identified in different solid tumors but not frequently in hematopoietic malignant cells. We investigated the presence of the Neurokinin-1 receptor in Acute Myeloid Leukemia cell lines (KG-1 and HL-60), demonstrating that Acute Myeloid Leukemia cell lines overexpress the truncated Neurokinin-1 receptor isoform compared with lymphocytes from healthy donors. Using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) method, we demonstrated that substance P induced cell proliferation in both Acute Myeloid Leukemia cell lines. We also observed that four different Neurokinin-1 receptor antagonists (L-733,060, L-732,138, CP 96–345 and aprepitant) elicited inhibition of Acute Myeloid Leukemia cell growth lines in a concentration-dependent manner, while growth inhibition was only marginal in lymphocytes; the specific antitumor action of Neurokinin-1 receptor antagonists occurs via the Neurokinin-1 receptor, and Leukemia cell death is due to apoptosis. Finally, administration of high doses of daily intraperitoneal fosaprepitant to NOD scid gamma mice previously xenografted with the HL60 cell line increased the median survival from 4 days (control group) to 7 days (treated group) ( p = 0.059). Taken together, these findings suggest that Neurokinin-1 receptor antagonists suppress leukemic cell growth and may be considered to be potential antitumor drugs for the treatment of human Acute Myeloid Leukemia.
Farhad Ravandi - One of the best experts on this subject based on the ideXlab platform.
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oral azacitidine maintenance therapy for Acute Myeloid Leukemia in first remission
The New England Journal of Medicine, 2020Co-Authors: Andrew Wei, Farhad Ravandi, Hartmut Dohner, Christopher Pocock, Pau Montesinos, Boris V Afanasyev, Herve Dombret, Hamid Sayar, Junho Jang, Kimmo PorkkaAbstract:Abstract Background Although induction chemotherapy results in remission in many older patients with Acute Myeloid Leukemia (AML), relapse is common and overall survival is poor. Methods We conduct...
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activity of decitabine as maintenance therapy in core binding factor Acute Myeloid Leukemia
Journal of Clinical Oncology, 2020Co-Authors: Mahran Shoukier, Farhad Ravandi, Naval Daver, Tapan M. Kadia, Hagop M Kantarjian, Guillermo Garciamanero, Keyur P Patel, Maro Ohanian, Ghayas C Issa, Jeffrey AldrichAbstract:7522Background: Real-time quantitative (RTPCR) based minimal residual disease (MRD) monitoring provides prognostic information in core binding factor Acute Myeloid Leukemia (CBF-AML). Earlier we re...
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Quizartinib in the treatment of FLT3-internal-tandem duplication-positive Acute Myeloid Leukemia.
Future Oncology, 2019Co-Authors: Shilpa Paul, Farhad Ravandi, Adam J Dipippo, Tapan M. KadiaAbstract:FLT3 mutations, characterized by an internal-tandem duplication or missense mutations in the tyrosine kinase domain, are observed in a third of patients with newly diagnosed Acute Myeloid Leukemia. FLT3-ITD mutations are associated with high relapse rates and short overall survival with conventional chemotherapy. Several tyrosine kinase inhibitors targeting FLT3 have been developed in an effort to improve survival and therapeutic options. This review focuses on quizartinib, a second-generation FLT3 inhibitor that has demonstrated efficacy and safety as a single agent and in combination with chemotherapy. We discuss its clinical development as well as its place in the treatment of FLT3-mutated Acute Myeloid Leukemia among the other FLT3 inhibtors currently available and its mechanisms of resistance.
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emerging treatment paradigms with flt3 inhibitors in Acute Myeloid Leukemia
Therapeutic advances in hematology, 2019Co-Authors: Nicholas J Short, Farhad Ravandi, Naval DaverAbstract:Mutations in the fms-like tyrosine kinase 3 (FLT3) gene are detected in approximately one-third of patients with newly diagnosed Acute Myeloid Leukemia (AML). These consist of the more common FLT3-...
Hartmut Dohner - One of the best experts on this subject based on the ideXlab platform.
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oral azacitidine maintenance therapy for Acute Myeloid Leukemia in first remission
The New England Journal of Medicine, 2020Co-Authors: Andrew Wei, Farhad Ravandi, Hartmut Dohner, Christopher Pocock, Pau Montesinos, Boris V Afanasyev, Herve Dombret, Hamid Sayar, Junho Jang, Kimmo PorkkaAbstract:Abstract Background Although induction chemotherapy results in remission in many older patients with Acute Myeloid Leukemia (AML), relapse is common and overall survival is poor. Methods We conduct...
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azacitidine and venetoclax in previously untreated Acute Myeloid Leukemia
The New England Journal of Medicine, 2020Co-Authors: Courtney D Dinardo, Hartmut Dohner, Brian A Jonas, Vinod Pullarkat, Michael J Thirman, Jacqueline S Garcia, Andrew Wei, Marina Konopleva, Anthony Letai, Pierre FenauxAbstract:Abstract Background Older patients with Acute Myeloid Leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising effica...
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circular rnas of the nucleophosmin npm1 gene in Acute Myeloid Leukemia
Haematologica, 2017Co-Authors: Susanne Hirsch, Peter Paschka, Verena I Gaidzik, Tamara J Blatte, Sarah Grasedieck, Sibylle Cocciardi, Arefeh Rouhi, Mojca Jongenlavrencic, Jan Kronke, Hartmut DohnerAbstract:In Acute Myeloid Leukemia, there is growing evidence for splicing pattern deregulation, including differential expression of linear splice isoforms of the commonly mutated gene nucleophosmin (NPM1). In this study, we detect circular RNAs of NPM1 and quantify circRNA hsa_circ_0075001 in a cohort of NPM1 wild-type and mutated Acute Myeloid Leukemia (n=46). Hsa_circ_0075001 expression correlates positively with total NPM1 expression, but is independent of the NPM1 mutational status. High versus low hsa_circ_0075001 expression defines patient subgroups characterized by distinct gene expression patterns, such as lower expression of components of the Toll-like receptor signaling pathway in high hsa_circ_0075001 expression cases. Global evaluation of circRNA expression in sorted healthy hematopoietic controls (n=10) and Acute Myeloid Leukemia (n=10) reveals circRNA transcripts for 47.9% of all highly expressed genes. While circRNA expression correlates globally with parental gene expression, we identify hematopoietic differentiation-associated as well as Acute Myeloid Leukemia subgroup-specific circRNA signatures.
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Acute Myeloid Leukemia with mutated nucleophosmin 1 an immunogenic Acute Myeloid Leukemia subtype and potential candidate for immune checkpoint inhibition
Haematologica, 2017Co-Authors: Jochen Greiner, Hartmut Dohner, Susanne Hofmann, Michael Schmitt, Marlies Gotz, M Wiesneth, Hubert Schrezenmeier, Donald Bunjes, Lars BullingerAbstract:Clinical and preclinical data suggest that Acute Myeloid Leukemia (AML) with mutated nucleophosmin 1 ( NPM1 mut) might constitute an immunogenic Leukemia subtype. In general, AML with NPM1 mut correlates with better prognosis, but the underlying mechanisms still remain to be elucidated. Our group
Peter Paschka - One of the best experts on this subject based on the ideXlab platform.
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circular rnas of the nucleophosmin npm1 gene in Acute Myeloid Leukemia
Haematologica, 2017Co-Authors: Susanne Hirsch, Peter Paschka, Verena I Gaidzik, Tamara J Blatte, Sarah Grasedieck, Sibylle Cocciardi, Arefeh Rouhi, Mojca Jongenlavrencic, Jan Kronke, Hartmut DohnerAbstract:In Acute Myeloid Leukemia, there is growing evidence for splicing pattern deregulation, including differential expression of linear splice isoforms of the commonly mutated gene nucleophosmin (NPM1). In this study, we detect circular RNAs of NPM1 and quantify circRNA hsa_circ_0075001 in a cohort of NPM1 wild-type and mutated Acute Myeloid Leukemia (n=46). Hsa_circ_0075001 expression correlates positively with total NPM1 expression, but is independent of the NPM1 mutational status. High versus low hsa_circ_0075001 expression defines patient subgroups characterized by distinct gene expression patterns, such as lower expression of components of the Toll-like receptor signaling pathway in high hsa_circ_0075001 expression cases. Global evaluation of circRNA expression in sorted healthy hematopoietic controls (n=10) and Acute Myeloid Leukemia (n=10) reveals circRNA transcripts for 47.9% of all highly expressed genes. While circRNA expression correlates globally with parental gene expression, we identify hematopoietic differentiation-associated as well as Acute Myeloid Leukemia subgroup-specific circRNA signatures.
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impact of salvage regimens on response and overall survival in Acute Myeloid Leukemia with induction failure
Leukemia, 2017Co-Authors: M Wattad, Peter Paschka, Verena I Gaidzik, Daniela Weber, Konstanze Dohner, Jurgen Krauter, Michael Heuser, Felicitas Thol, Thomas Kindler, Michael LubbertAbstract:Impact of salvage regimens on response and overall survival in Acute Myeloid Leukemia with induction failure
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asxl1 mutations in younger adult patients with Acute Myeloid Leukemia a study by the german austrian Acute Myeloid Leukemia study group
Haematologica, 2015Co-Authors: Peter Paschka, Richard F Schlenk, Verena I Gaidzik, Julia K Herzig, Teresa Aulitzky, Lars Bullinger, Daniela Spath, Veronika Teleanu, Andrea Kundgen, Claushenning KohneAbstract:We studied 1696 patients (18 to 61 years) with Acute Myeloid Leukemia for ASXL1 mutations and identified these mutations in 103 (6.1%) patients. ASXL1 mutations were associated with older age (P<0.0001), male sex (P=0.041), secondary Acute Myeloid Leukemia (P<0.0001), and lower values for bone marrow (P<0.0001) and circulating (P<0.0001) blasts. ASXL1 mutations occurred in all cytogenetic risk-groups; normal karyotype (40%), other intermediate-risk cytogenetics (26%), high-risk (24%) and low-risk (10%) cytogenetics. ASXL1 mutations were associated with RUNX1 (P<0.0001) and IDH2(R140) mutations (P=0.007), whereas there was an inverse correlation with NPM1 (P<0.0001), FLT3-ITD (P=0.0002), and DNMT3A (P=0.02) mutations. Patients with ASXL1 mutations had a lower complete remission rate (56% versus 74%; P=0.0002), and both inferior event-free survival (at 5 years: 15.9% versus 29.0%; P=0.02) and overall survival (at 5 years: 30.3% versus 45.7%; P=0.0004) compared to patients with wildtype ASXL1. In multivariable analyses, ASXL1 and RUNX1 mutation as a single variable did not have a significant impact on prognosis. However, we observed a significant interaction (P=0.04) for these mutations, in that patients with the genotype ASXL1(mutated)/RUNX1(mutated) had a higher risk of death (hazard ratio 1.8) compared to patients without this genotype. ASXL1 mutation, particularly in the context of a coexisting RUNX1 mutation, constitutes a strong adverse prognostic factor in Acute Myeloid Leukemia.