Dendritic cells in MDS and AML – cause, effect or solution to the immune pathogenesis of disease?

Abstract

In a recent issue of Leukemia, Ma et al1 characterised the absolute numbers of both myeloid and plasmacytoid DC in the peripheral blood of patients with myelodysplastic syndromes (MDS) and showed that both populations were derived from the malignant clone but were present in reduced numbers compared with those of normal blood. Likewise, both DC subsets have been identified in patients with acute myeloid leukaemia (AML) and three subgroups of patients were characterised according to the percentage of cells of different DC subsets present in the separated mononuclear cells from the blood of these patients.2 However, in contrast with the study by Ma et al, in the blood of patients with AML the identification of DC subsets by surface immunophenotype can be difficult due to the inherent nature of the disease itself. Hence, leukaemic blasts may be misidentified as DC and, similarly, the aberrant expression of surface markers in AML may result in 'DC-associated markers' on leukaemic blasts that are not DC. When considering these problems, as well as the fact that approximately 60–80% of primary AML samples may generate DC in in vitro culture, one might classify AML, and MDS, as a type of bone marrow malignancy derived from DC precursors. These AML-derived DC (AML-DC) arise from the leukaemic clone3,4,5 and, thus, may express leukaemic antigens. Hence, AML-specific and patient-specific AML-DC may be generated for potential use in the immune therapy of AML. However, the DC generated from leukaemic blasts are part of the malignancy and malignant cells may produce 'tolerogenic' signals (such as the type 2 cytokine IL-10) which promote tumorigenesis. It is unclear if these in vitro-generated AML-DC also produce 'tolerogenic' signals. In considering these AML-DC for the potential immunotherapy of AML, it would be important to identify whether these 'tumorigenic' signals are inherent to the tumour cells and any derivatives thereof – an outcome that could be detrimental in the directed use of these cells for anti-tumour immunity.6