Flt-3 internal tandem duplication hampers differentiation of AML blasts towards leukemic dendritic cells

Houtenbos, Ilse; Westers, Theresia M.; Ossenkoppele, Gert J.; Loosdrecht, Arjan A. van de; Hess, Corine J.; Waisfisz, Quinten

doi:10.1038/sj.leu.2404348

Cited by 16 publications

(13 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Firstly, in accordance with our previous work, AML-DC vaccination is potentially applicable in the majority of AML patients as shown by successful AML-DC cultures in 64% (9/14) of AML samples Houtenbos et al, 2006b). AML-DC differentiation inducibility was successfully predicted by the expression of CD14 and CD120a in combination with Flt-3 ITD status in this patient group (Table 1).…”

Section: Feasibility Of Preparing Aml-dc For Clinical Vaccinationsupporting

confidence: 86%

“…b AML-DC differentiation was evaluated by immunophenotypic analysis. As previously described a cut-off value of 10% discriminated between successful and unsuccessful AML-DC cultures (Houtenbos et al, 2006b). c Differentiation inducibility of AML blasts can be predicted, as previously described, by the following formula (Houtenbos et al, 2006b): Probability (differentiation towards AML-DC):…”

Section: Feasibility Of Preparing Aml-dc For Clinical Vaccinationmentioning

confidence: 99%

“…The expression of CD14, TNFa-RI (CD120a) as well as the absence of Flt-3 internal tandem duplication (ITD) are highly associated with DC differentiation inducibility of AML blasts, enabling patient selection prior to DC culture (Houtenbos et al, 2004. In a prospective analysis a predictive model incorporating these parameters exhibited a high sensitivity and specificity (Houtenbos et al, 2006b). Based on these data we started a phase I/II clinical trial using AML-DC vaccines.…”

Section: Clinical Vaccination Strategy With Leukemia-derived DCmentioning

confidence: 99%

See 2 more Smart Citations

Feasibility of clinical dendritic cell vaccination in acute myeloid leukemia

et al. 2006

View full text Add to dashboard Cite

Section: Feasibility Of Preparing Aml-dc For Clinical Vaccinationsupporting

confidence: 86%

Section: Feasibility Of Preparing Aml-dc For Clinical Vaccinationmentioning

confidence: 99%

Section: Clinical Vaccination Strategy With Leukemia-derived DCmentioning

confidence: 99%

See 1 more Smart Citation

Feasibility of clinical dendritic cell vaccination in acute myeloid leukemia

et al. 2006

View full text Add to dashboard Cite

“…14 All AML subgroups seem to be eligible for the generation of DC, as we could not see significant differences in the differentiating capacity of DC in cytogenetic risk or FAB groups, supporting the data of others and us. 47 The most interesting results of the present work were, that the average harvest of DC and DC subtypes were comparable with all methods used. This means, that all of these methods are principally suitable to generate DC; however, and this was the second interesting result, not every given case of AML can be differentiated to DC with 1 selected method.…”

Section: Generation Quantification and Characterization Of Leukemiasupporting

confidence: 61%

Dendritic Cells (DCs) Can Be Successfully Generated From Leukemic Blasts in Individual Patients With AML or MDS

Kremser¹,

Dressig²,

Grabrucker³

et al. 2010

Journal of Immunotherapy

View full text Add to dashboard Cite

Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.

show abstract

“…77 A practical draw-back of this approach is that Leukemia derived DCs can only be generated from a minority of patients, as FLT-ITD mutations or a lack of CD14 expressed on blasts prevent the maturation to the DC phenotype. 78,79 Enhancing response to vaccination A critical factor to consider in designing clinical trials evaluating dendritic cell vaccines is the immunologic milieu into which the vaccine is being administered. Tumor induced immune suppression may blunt immune response to vaccination in patients with advanced disease.…”

Section: Leukemia Derived Dendritic Cellsmentioning

confidence: 99%