Objective(s): Mutant forms FMS-like tyrosine kinase-3 (FLT3), are reported in 25% of childhood acute lymphoid leukemia (ALL) and 30% of acute myeloid leukemia (AML) patients. In this study, drug response, growth promoting, and protein trafficking of FLT3 wild-type was compared with two active mutants (Internal Tandem Duplication (ITD)) and D835Y. Materials and Methods:FLT3 was expressed on fact...

Sensitivity to changes in the interaural time difference (ITD) of 50 msec tones was measured in single units in the inferior colliculus of urethane-anesthetized guinea pigs. ITD functions were measured with 100 repeats and fine spacing (100 points per cycle). The just noticeable difference (jnd) for ITD was determined using receiver operating characteristic (ROC) analysis of the spike-count dis...

Mutation of the fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD), which is one of the most frequent genetic alterations, strongly contributes to an increased risk of treatment failure and to poor prognosis. In this study, we established quantitative fragment analysis of FLT3-ITD simultaneously measuring mutant allele burden and length, verified the analytical performance and ev...

BACKGROUND High white blood cell count at presentation is an unfavorable prognostic factor for treatment outcome in intermediate cytogenetic risk acute myeloid leukemia. Since the impact of white blood cell count on outcome of subgroups defined by the molecular markers NPMc(+) and FLT3-internal tandem duplication (ITD) is unknown, we addressed this issue. DESIGN AND METHODS We studied the eff...

Constitutive activation of FMS-like tyrosine kinase 3 (FLT3) by internal tandem duplication (ITD) mutations is one of the most common molecular alterations known in acute myeloid leukemia (AML). To investigate the role FLT3/ITD mutations play in the development of leukemia, we generated a FLT3/ITD knock-in mouse model by inserting an ITD mutation into the juxtamembrane domain of murine Flt3. FL...

PURPOSE Gemtuzumab ozogamicin (GO), a calicheamicin-conjugated mAb against CD33, has been used in the treatment of acute myeloid leukemia (AML). We evaluated the impact of the addition of GO to standard chemotherapy and hematopoietic stem cell transplant (HCT) in patients withFLT3/ITD. EXPERIMENTAL DESIGN We analyzed children withFLT3/ITD-positive AML (n= 183) treated on two consecutive Child...

In birds and mammals, precisely timed spikes encode the timing of acoustic stimuli, and interaural acoustic disparities propagate to binaural processing centers. The Jeffress model proposes that these projections act as delay lines to innervate an array of coincidence detectors, every element of which has a different relative delay between its ipsilateral and contralateral excitatory inputs. Th...

Bilateral cochlear implantation attempts to increase performance over a monaural prosthesis by harnessing the binaural processing of the auditory system. Although many bilaterally implanted human subjects discriminate interaural time differences (ITDs), a major cue for sound localization and signal detection in noise, their performance is typically poorer than that of normal-hearing listeners. ...

The MLL-partial tandem duplication (PTD) associates with high-risk cytogenetically normal acute myeloid leukemia (AML). Concurrent presence of FLT3-internal tandem duplication (ITD) is observed in 25% of patients with MLL-PTD AML. However, mice expressing either Mll-PTD or Flt3-ITD do not develop AML, suggesting that 2 mutations are necessary for the AML phenotype. Thus, we generated a mouse ex...

The roles of interaural time difference (ITD) and interaural level difference (ILD) were studied in free-field source localization experiments for sine tones of low frequency (250-750 Hz). Experiments combined real-source trials with virtual trials created through transaural synthesis based on real-time ear canal measurements. Experiments showed the following: (1) The naturally occurring ILD is...