Christian Thiede

..In conclusion, NPM1 mutations represent a common genetic abnormality in adult AML. If not associated with FLT3-ITD mutations, mutant NPM1 appears to identify patients with improved response toward treatment...

..In addition, the potential impact of novel procedures, e.g. subset chimerism or real-time PCR-based procedures, is discussed...

..Constitutive activation may be associated with monocytoid differentiation. A high mutant/wt ratio in ITD-positive patients appears to have a major impact on the prognostic relevance...

..Monitoring of CD34(+) donor chimerism in the peripheral blood allows prediction of imminent relapse after allogeneic stem cell transplantation even when a disease-specific marker is lacking...

..The aim of this study was to evaluate the impact of FLT3-ITD on cell proliferation and CXCR4-dependent migration in human hematopoietic progenitor cells and to investigate their response to CXCR4 inhibition...

..This trial was registered at www.clinicaltrials.gov as #NCT00460629...

..Although associated with inferior disease-free survival, the results of this study do not unequivocally support the notion that MLL PTD mutations represent an independent prognostic factor...

..We hypothesized that this mechanism applies to extramedullary AML relapse which occurs frequently after allogeneic HSCT and might also not be restricted to haploidentical HSCT...

..We hypothesized that GO might be safe and effective as part of a reduced-intensity conditioning regimen as salvage therapy of CD33+ acute myeloid leukemia...

..The purpose of this study was to investigate whether further biological characterization of the HLA-DR(neg) acute myeloid leukemia patients would allow more clearly define criteria to separate APL from non-APL patients...

..Further optimisation, probably involving less T cell depletion, is necessary before a randomized comparison with standard conditioning can be planned...

..5%, 30%, 10.6%, and 3.3%, respectively. The risk model allows further stratification of patients with intermediate-risk karyotype into 2 prognostic groups with implications for the therapeutic strategy...

..To assess the optimal cumulative dose of cytarabine for treatment of young adults with acute myeloid leukemia (AML) within a prospective multicenter treatment trial...

..We assessed the prognostic value of the new risk classification in a large cohort of patients...

..Our study shows that resistance gene expression should be considered together with age, cytogenetics and FLT3 mutational status for risk-adapted treatment strategies in AML in the future...

..Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens...

..Both number and origin (donor vs. host) of dendritic cells (DC) are associated with acute graft-versus-host disease (aGvHD), relapse and graft failure after human allogeneic hematopoietic cell transplantation (aHCT)...

..1% in cases without this morphology (p=0.001). There was no influence on response to treatment or survival. Therefore, cup-like nuclear morphology is an indicator of normal karyotype and should guide more specific molecular analyses...

..In summary, resistance against PKC412 appears to be mediated by up-regulation of anti-apoptotic genes and down-regulation of proapoptotic signals as well as genes that are involved in normal and malignant hematopoiesis...

..We sought to determine whether donor type is a prognostic factor in elderly patients in the era of high-resolution DNA-based HLA typing...

..The importance of these markers in prediction models for GVHD and relapse remain to be defined in large prospective clinical trials...

..Together, these data show that the expansion of CD34+ cord blood cells in a culture system containing a three-dimensional collagen I matrix induces a qualitative change in the gene-expression profile of cultivated HSCs...

..This could be due to alternative initiating events for activation of the RAS pathway like constitutive tyrosine kinase activation or mutations in Ras-regulating genes...

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..Based on our data and the immature glycosylation pattern of FLT3-ITD, we speculate that the mutant protein resides most probably in an unidentified compartment of the secretory pathway between the ER and the Golgi apparatus...

..These results suggest a novel and unexpected role for members of the NFAT transcription factor family in the hematopoietic system...

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..Based on these encouraging results, further studies of fludarabine and targeted busulfan are warranted in standard-risk patients...

..Whether this will ultimately improve the survival of patients with leukemia after transplantation has to be shown in prospective studies...

..These methods will facilitate work to understand the linkage between personal variations and disease propensity, as well as possibilities for personal genome surgery...

..To evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in a series of patients with inherited complete IFN-gamma receptor 1 (IFNgammaR1) deficiency...

..Loss of a critical segment of 9q, most likely in 9q22, and disruption of CEBPA function possibly cooperate in the pathogenesis of del(9q) AML...

..Taken together, RGS2 is a novel mediator of myeloid differentiation, and its repression is an important event in Flt3-ITD-induced transformation...

..A peptide nucleic acid (PNA)-based technique was used on 232 AML samples to detect point mutations of the hotspots in N-RAS and K-RAS. No significant correlations between RAS mutations and clinical features, karyotype or FLT3 were found...

..In conclusion, the regimen itself can be carried out safely in patients with relative contraindications against myeloablative conditioning. However, GVHD causes significant non-relapse mortality in high risk patients...

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..These results suggest that it may be useful to determine the exact kind of FLT3 mutation when applying receptor kinase inhibitors in clinical trials...

..Indeed strong signal transducers and activators of transcription 5 (STAT5) activation could only be demonstrated for FLT3-ITDs...

..The close relation (P = 0.0075) between the first occurrence of graft-vs.-host disease and the complete clearance of bcr/abl positive blood cells argues in favour of an effective graft-vs.-leukaemia reaction...

..This model fits with the hypothesis that NPMc(+) acute myeloid leukemia arises from an NPM1 mutation with haploinsufficiency of the wild-type NPM1 allele...

..RAS mutations occur in 12% to 27% of patients with acute myeloid leukemia (AML) and enhance sensitivity to cytarabine in vitro. We examined whether RAS mutations impact response to cytarabine in vivo...

..All but one of the reported cases have occurred in pediatric patients and six of those patients died, suggesting that this may be a rare but frequently fatal complication of pediatric allogeneic stem cell transplant...

..Liver disease has not further deteriorated. This experience shows that correction of IFNgammaR1 deficiency is possible by BMT and complications of the disease can be controlled...

..6% (p<0.01). Moreover, JAK2 V617F mutations in CBF leukemias were associated with an aggressive clinical course with 80% of the patients relapsing...

..We found B-cell monoclonality to be a more frequent than expected finding in gastritis and to be strongly associated with the presence of lymphoid follicles; thus, its presence is of little significance in patient management...

..Therefore, we established a new isocratic HPLC method, which sensitively detects PKC412 and five of its metabolites...

..Our data support a reassessment of the WHO classification in the light of a more biologic understanding of AML. This study is registered at www.ClinicalTrials.gov as #NCT00180115...

..Nonetheless, the presence of two or more miRNA binding sites within the mRNA was usually associated with a decrease in mRNA levels. Taken together, these findings provide evidence that specific miRNA expression patterns exist in AML...

..We tracked the long-term stability of remissions in this prospective, multicenter trial...

..We conclude that even if trace amounts of MSC are co-transplanted during PBSCT or BMT, they do not expand significantly in the host bone marrow...

..Therefore, telomere length might serve as a prognostic marker for AML patients. These findings would have to be confirmed in large, prospective studies...