نتایج جستجو برای: ژن flt3

تعداد نتایج: 19081  

Journal: :Blood 2009
Keith W Pratz Jorge Cortes Gail J Roboz Niranjan Rao Omotayo Arowojolu Adam Stine Yukimasa Shiotsu Aiko Shudo Shiro Akinaga Donald Small Judith E Karp Mark Levis

Internal tandem duplication mutations of FLT3 (FLT3/ITD mutations) are common in acute myeloid leukemia (AML) and confer a poor prognosis. This would suggest that FLT3 is an ideal therapeutic target, but FLT3 targeted therapy has produced only modest benefits in clinical trials. Due to technical obstacles, the assessment of target inhibition in patients treated with FLT3 inhibitors has been lim...

Journal: :Molecular cancer therapeutics 2012
Kristin Pietschmann Hella Anna Bolck Marc Buchwald Steffi Spielberg Harald Polzer Karsten Spiekermann Gesine Bug Thorsten Heinzel Frank-Dietmar Böhmer Oliver H Krämer

Activating mutations of the class III receptor tyrosine kinase FLT3 are the most frequent molecular aberration in acute myeloid leukemia (AML). Mutant FLT3 accelerates proliferation, suppresses apoptosis, and correlates with poor prognosis. Therefore, it is a promising therapeutic target. Here, we show that RNA interference against FLT3 with an internal tandem duplication (FLT3-ITD) potentiates...

Journal: :Blood 2012
Samuel J Taylor Samantha A Dagger Christine B F Thien Matthew E Wikstrom Wallace Y Langdon

High levels of expression of wild-type Flt3 characterize many hematopoietic proliferative diseases and neoplasms, providing a potential therapeutic target. Using the c-Cbl RING finger mutant mouse as a model of a myeloproliferative disease (MPD) driven by wild-type Flt3, in the present study, we show that treatment with the Flt3 kinase inhibitor AC220 blocks MPD development by targeting Flt3(+)...

2016
Colleen M. Lau Simone A. Nish Nir Yogev Ari Waisman Steven L. Reiner Boris Reizis

A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L admi...

2015
Silvia Sironi Michaela Wagner Alexander Kuett Heidrun Drolle Harald Polzer Karsten Spiekermann Christina Rieger Michael Fiegl

Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase constitutively expressed by acute myeloid leukaemia (AML) blasts. In addition, 25% of AML patients harbour a FLT3-ITD mutation, associated with inferior outcome due to increased relapse rate. Relapse might be propagated by interactions between AML blasts and the bone marrow microenvironment. Besides cellular elements of the microen...

Journal: :Blood 2013
Eric I Zimmerman David C Turner Jassada Buaboonnam Shuiying Hu Shelley Orwick Michael S Roberts Laura J Janke Abhijit Ramachandran Clinton F Stewart Hiroto Inaba Sharyn D Baker

FLT3 kinase internal tandem duplication (ITD) mutations are common in acute myeloid leukemia (AML) and are associated with poor clinical outcomes. Although initial responses to FLT3 tyrosine kinase inhibitors (TKIs) are observed in FLT3-ITD-positive patients, subsequent relapse often occurs upon acquisition of secondary FLT3 kinase domain (KD) mutations, primarily at residues D835 and F691. Usi...

2016
Amanda M. Smith Matthew D. Dun Erwin M. Lee Celeste Harrison Richard Kahl Hayley Flanagan Nikita Panicker Baratali Mashkani Anthony S. Don Jonathan Morris Hamish Toop Richard B. Lock Jason A. Powell Daniel Thomas Mark A. Guthridge Andrew Moore Leonie K. Ashman Kathryn A. Skelding Anoop Enjeti Nicole M. Verrills

Constitutive activation of the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3), via co-expression of its ligand or by genetic mutation, is common in acute myeloid leukemia (AML). In this study we show that FLT3 activation inhibits the activity of the tumor suppressor, protein phosphatase 2A (PP2A). Using BaF3 cells transduced with wildtype or mutant FLT3, we show that FLT3-induced PP...

2017
Narges Rezaei Nargess Arandi Behnaz Valibeigi Sezaneh Haghpanah Mehdi Khansalar Mani Ramzi

OBJECTIVE In this study, we evaluated the frequency of FMS-like tyrosine kinase 3 (FLT3-ITD and FLT3-TKD) and nucleophosmin (NPM1) mutations in Iranian patients with cytogenetically normal acute myeloid leukemia (CN-AML). The clinical and laboratory characteristics were compared between wild-type and mutant cases. MATERIALS AND METHODS Seventy newly diagnosed de novo AML patients were recruit...

Journal: :Blood 1997
I Rappold B L Ziegler I Köhler S Marchetto O Rosnet D Birnbaum P J Simmons A C Zannettino B Hill S Neu W Knapp R Alitalo K Alitalo A Ullrich L Kanz H J Bühring

The class III receptor tyrosine kinase FLT3/FLK2 (FLT3; CD135) represents an important molecule involved in early steps of hematopoiesis. Here we compare cell-surface expression of FLT3 on bone marrow (BM) and cord blood (CB) cells using monoclonal antibodies (MoAbs) specific for the extracellular domain of human FLT3. Flow cytometric analysis of MACS-purified BM and CB cells showed that 63% to...

2014
Kristin K. Deeb Matthew T. Smonskey HanChun DeFedericis George Deeb Sheila N.J. Sait Meir Wetzler Eunice S. Wang Petr Starostik

In contrast to FLT3 ITD mutations, in-frame deletions in the FLT3 gene have rarely been described in adult acute leukemia. We report two cases of AML with uncommon in-frame mutations in the juxtamembrane domain of the FLT3 gene: a 3-bp (c.1770_1774delCTACGinsGT; p.F590_V592delinsLF) deletion/insertion and a 12-bp (c.1780_1791delTTCAGAGAATAT; p.F594_Y597del) deletion. We verified by sequencing t...

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