The type III receptor tyrosine kinase fms-like tyrosine kinase 3 (FLT3) is expressed on both normal hematopoietic stem cells and acute myeloid leukemia (AML) cells and regulates their proliferation. Internal tandem duplication (ITD) mutation of FLT3 is present in a third of AML cases, results in constitutive activation and aberrant signaling of FLT3, and is associated with adverse treatment out...

Bilateral cochlear implantation seeks to improve hearing by taking advantage of the binaural processing of the central auditory system. Cochlear implants typically encode sound in each spectral channel by amplitude modulating (AM) a fixed-rate pulse train, thus interaural time differences (ITD) are only delivered in the envelope. We investigated the ITD sensitivity of inferior colliculus (IC) n...

Internal tandem duplication (ITD) mutations in the Fms-related tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor prognosis in patients with acute myeloid leukemia (AML). Due to the development of drug resistance, few FLT3-ITD inhibitors are effective against FLT3-ITD+ AML. In this study, we show that FLT3-ITD activates a novel pathway involving p21Cdkn1a (p21) and pre-B cell leu...

Objectives: Bilateral cochlear implant (CI) listeners currently use stimulation strategies which encode interaural time differences (ITD) in the temporal envelope but which do not transmit ITD in the fine structure, due to the constant phase in the electrical pulse train. To determine the utility of encoding ITD in the fine structure, ITD-based lateralization was investigated with four CI liste...

Internal tandem duplication mutations in the Flt3 tyrosine kinase gene (ITD-Flt3) and overexpression of Survivin are frequently found in patients with acute myeloid leukemia (AML). We investigated whether Survivin mediates the enhanced survival of primary hematopoietic progenitor cells (HPCs) resulting from ITD-Flt3 signaling. Ectopic ITD-Flt3 mutants increased Survivin expression in Ba/F3 cell...

Human sound source localization relies on various acoustical cues one of the most important being the interaural time difference (ITD). ITD is best detected in the fine structure of low-frequency sounds but it may also contribute to spatial hearing at higher frequencies if extracted from the sound envelope. The human brain mechanisms related to this envelope ITD cue remain unexplored. Here, we ...

objective(s):sulfur mustard (sm) was used by the iraqi army against the iranian troops in the iran-iraq war from 1983–1988. this chemical gas affects different organs including the skin, lungs and the hematopoietic system. any exposure to sm increases the risk of chromosomal breaking, hyperdiploidy and hypodiploidy. studies have shown that the risk for acute myeloblastic and lymphoblastic leuke...

Individualized Treatment Strategy with Small-Molecular Inhibitors in Acute Myeloid Leukemia with Concurrent FLT3-ITD and FLT3-TKD Mutation Harald Polzer1-4*, Hanna Janke1,2, Stephanie Schneider1, Wolfgang Hiddemann1-4, Marion Subklewe1 and Karsten Spiekermann1-4 1Department of Internal Medicine III, University Hospital Großhadern, Ludwig-Maximilians-University Munich, Germany 2Clinical Cooperat...