نتایج جستجو برای: flt3 itd

تعداد نتایج: 4119  

2017
Bao Nguyen Allen B. Williams David J. Young Hayley Ma Li Li Mark Levis Patrick Brown Donald Small

Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that normally functions in hematopoietic cell survival, proliferation and differentiation. Constitutively activating mutations of FLT3 map predominately to the juxtamembrane domain (internal tandem duplications; ITD) or the activation loop (AL) of the kinase domain and are detected in about 1/3 of de novo acute myeloid leukemia (AM...

Journal: :Blood 2008
Lars Bullinger Konstanze Döhner Raphael Kranz Christoph Stirner Stefan Fröhling Claudia Scholl Young H Kim Richard F Schlenk Robert Tibshirani Hartmut Döhner Jonathan R Pollack

Acute myeloid leukemia with normal karyotype (NK-AML) represents a cytogenetic grouping with intermediate prognosis but substantial molecular and clinical heterogeneity. Within this subgroup, presence of FLT3 (FMS-like tyrosine kinase 3) internal tandem duplication (ITD) mutation predicts less favorable outcome. The goal of our study was to discover gene-expression patterns correlated with FLT3...

2015
Ayako Nogami Gaku Oshikawa Keigo Okada Shusaku Fukutake Yoshihiro Umezawa Toshikage Nagao Tetsuya Kurosu Osamu Miura

FLT3-ITD and FLT3-TKD are the most frequent tyrosine kinase mutations in acute myeloid leukemia (AML), with the former associated with poor prognosis. Here, we show that the PI3K inhibitor GDC-0941 or the Akt inhibitor MK-2206 induced apoptosis through the mitochondria-mediated intrinsic pathway more efficiently in hematopoietic 32D cells driven by FLT3-TKD (32D/TKD) than FLT3-ITD (32D/ITD), wh...

2016
Kshama A. Doshi Rossana Trotta Karthika Natarajan Feyruz V. Rassool Adriana E. Tron Dennis Huszar Danilo Perrotti Maria R. Baer

Internal tandem duplication of fms-like tyrosine kinase-3 (FLT3-ITD) is frequent (30 percent) in acute myeloid leukemia (AML), and is associated with short disease-free survival following chemotherapy. The serine threonine kinase Pim-1 is a pro-survival oncogene transcriptionally upregulated by FLT3-ITD that also promotes its signaling in a positive feedback loop. Thus inhibiting Pim-1 represen...

Journal: :American journal of clinical pathology 2008
Veronica Rausei-Mills Karen L Chang Karl K Gaal Lawrence M Weiss Qin Huang

Acute myeloid leukemia (AML) with normal cytogenetics represents approximately 40% to 50% of de novo AML. This heterogeneous AML subgroup constitutes the single largest cytogenetic group with an intermediate prognosis. Previous studies have suggested that the Fms-like tyrosine kinase-3 internal tandem duplication (FLT3/ITD) mutation-positive de novo AML may represent a distinctive subgroup of A...

Journal: :Blood 2012
Sarah Greenblatt Li Li Christopher Slape Bao Nguyen Rachel Novak Amy Duffield David Huso Stephen Desiderio Michael J Borowitz Peter Aplan Donald Small

Constitutive activation of FLT3 by internal tandem duplication (ITD) is one of the most common molecular alterations in acute myeloid leukemia (AML). FLT3/ITD mutations have also been observed in myelodysplastic syndrome patients both before and during progression to AML. Previous work has shown that insertion of an FLT3/ITD mutation into the murine Flt3 gene induces a myeloproliferative neopla...

2014
Grzegorz Helbig Krzysztof Wozniczka Agnieszka Wieclawek Anna Soja Aleksandra Bartkowska-Chrobok Slawomira Kyrcz-Krzemien

AIM OF THE STUDY Mutant NPM1 and CEBPA have been reported in patients with acute myeloid leukaemia (AML) and intermediate cytogenetic risk, and they appear to be associated with characteristic demographic and laboratory data, as well as clinical outcome. The objective of the study was to assess the clinical relevance of NPM1 and CEBPA mutations in AML. MATERIAL AND METHODS This retrospective ...

Journal: :Blood 2004
Mark Levis Rosalyn Pham B Douglas Smith Donald Small

Patients with acute myeloid leukemia (AML) harboring internal tandem duplication mutations of the FLT3 receptor (FLT3/ITD mutations) have a poor prognosis compared to patients lacking such mutations. Incorporation of FLT3 inhibitors into existing chemotherapeutic regimens has the potential to improve clinical outcomes in this high-risk group of patients. CEP-701, an indolocarbazole-derived sele...

Journal: :Biochemical Pharmacology 2021

• Structural aspects of the FLT3 receptor in signalling. Clonal evolution mutants. Recurrent mutations and its regulation signalling cascade drug therapy. Acute myelogenous leukaemia (AML) is an aggressive blood cancer characterized by rapid proliferation immature myeloid blast cells, resulting a high mortality rate. The 5-year overall survival rate for AML patients approximately 25%. Circa 35%...

2017
Anne-Kathrin Garz Saskia Wolf Sonja Grath Verena Gaidzik Stefan Habringer Binje Vick Martina Rudelius Christoph Ziegenhain Sylvia Herold Marie-Theresa Weickert Martha Smets Christian Peschel Robert A.J. Oostendorp Sebastian Bultmann Irmela Jeremias Christian Thiede Konstanze Döhner Ulrich Keller Katharina S. Götze

Effectively targeting leukemia-initiating cells (LIC) in FLT3-ITD-mutated acute myeloid leukemia (AML) is crucial for cure. Tyrosine kinase inhibitors (TKI) have limited impact as single agents, failing to eradicate LIC in the bone marrow. Using primary AML samples and a patient-derived xenograft model, we investigated whether combining the FLT3-selective TKI crenolanib with the hypomethylating...

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