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Identification of CD14 as a predictor for leukemic dendritic cell differentiation in acute myeloid leukemia

Leukemia volume 17, pages 1683–1684 (2003)Cite this article

TO THE EDITOR

Mohty et al1 reported that circulating leukemic myeloid blood dendritic cells (MDCs) and CD14+ cells of acute myeloid leukemia (AML) patients represent the leukemic compartments that can be induced in vitro to acquire the mature dendritic cell (DC) phenotype in the presence of GM-CSF, IL-4 and CD40L. In contrast, culture of the CD14− subpopulations did not result in the generation of leukemic DC. In our laboratory, we generate leukemic DC from AML blasts by the use of a cytokine cocktail.2 We also observed a correlation between the percentage of CD14 expression on AML blasts and AML-DC culture outcome, as defined by the percentage of CD40+/CD86+ cells at the end of culture (n=33, Spearman's ρ : 0.51, P=0.002). In contrast to Mohty et al, we were able to culture leukemic DC in 5/19 (26%) of the CD14− AML patients. The discrepancy between these observations could be related to several aspects. Firstly, in our immunophenotypic analysis we gated specifically on the CD45dim blast population, resulting in a well-defined leukemic blast population. Secondly, the culture method used by Mohty et al, is typically used to culture monocyte-derived DC.3,4 We observed that it is more effective to use an alternative culture method for the induction of DC differentiation in AML samples. We use a combination of various cytokines, namely, GM-CSF, TNF-α, SCF, Flt3-L, IL-3 and IL-4 resulting in functionally active (as measured by mixed lymphocyte reaction) leukemic DCs in 14 days. Additionally, a culture method based on the use of calcium ionophores (CI), thereby bypassing receptor-mediated signaling, is able to further increase the percentage of successful AML-DC cultures, even in CD14− AML samples.2 In a population of 33 AML patients, blasts of 19 (58%) patients showed less than 15% CD14 expression. In five (26%) AML samples, we were able to generate leukemic DC by the use of the described cytokine cocktail. More importantly, by culturing AML blasts with the CI A23187 and IL-4 for only 2 days, we generated mature functionally active leukemic DC in 10 out of 15 CD14− AML samples tested (Table 1). Recently, we have shown that serum-free culture of AML-DC is feasible and that these DC are comparable to serum-enriched cultured AML-DC with regard to morphological, immunophenotypical and functional characteristics.5 Overall, these results indicate that the serum-free culture of AML-DC derived from CD14− AML blasts, by the use of CI, is feasible in 71% of the AML patients. The use of CI provides an excellent alternative method for the induction of DC differentiation in CD14− AML samples, thus enabling the development of vaccination programs for this subgroup of AML patients.

Table 1 Successful generation of CD40+/CD86+ leukemic DC from CD14+ and CD14− AML samples using two different culture methods
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References

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  1. Department of Hematology, VU University Medical Center, De Boelelaan, HV Amsterdam, The Netherlands

    I Houtenbos, T M Westers, G J Ossenkoppele & A A van de Loosdrecht

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  1. I Houtenbos
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  2. T M Westers
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  3. G J Ossenkoppele
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  4. A A van de Loosdrecht
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Houtenbos, I., Westers, T., Ossenkoppele, G. et al. Identification of CD14 as a predictor for leukemic dendritic cell differentiation in acute myeloid leukemia. Leukemia 17, 1683–1684 (2003). https://doi.org/10.1038/sj.leu.2403014

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