The monocyte system in haematological malignancies

Abstract

Monocytes consist of classical, intermediate, and non-classical monocytes. In haematological malignancies, such as multiple myeloma and acute myeloid leukaemia, monocytes are affected by both the disease itself and the treatment patients receive. The overall aim of this thesis was to explore monocyte subpopulations in clinical settings of haematological malignancies by (i) elucidating the important pre-analytical factors to properly identify the subsets, (ii) monitoring monocyte regeneration after stem cell transplantation in patients with haematological malignancies, and (iii) investigating the effects of immunomodulatory drugs on metabolism and cytokine secretion. We demonstrated that K2EDTA, ACD-A, and Li-Heparin blood sampling tubes perform similarly regarding the distribution of monocyte subpopulations. In contrast, both the monocyte concentration and relative values could be significantly affected by choice of blood sampling tubes and decreased sample volume. Our results demonstrate that monocytes regenerate very early after stem cell transplantation, before the normalisation of other cell populations. This is true for multiple myeloma patients, as well for patients with other haematological malignancies, mainly acute myeloid leukaemia. The immunomodulatory drugs thalidomide, lenalidomide, and pomalidomide, which are therapeutically important in haematological malignancies, altered monocyte metabolism, especially when cells were cultured with LPS. Lenalidomide had a stronger effect on monocyte metabolism than the other two drugs. Furthermore, all three drugs decreased TLR4-induced mediator release, with the strongest effect for pomalidomide, whereas lenalidomide, and especially, thalidomide, had weaker effects. In conclusion, carefully standardizing blood sampling procedures is important to further develop monocyte analysis as a clinical tool, and the associations between monocyte subset variations and various diseases suggest additional studies should be conducted to clarify whether the analysis of monocyte subsets should be incorporated into routine clinical handling. IMiDs can alter monocyte metabolism and communication, but the strength of these effects differs between the IMiDs.