Midtveisevaluering - Ida Marie Rundgren

ABSTRAKT

THE MONOCYTE SYSTEM IN HEMATOLOGICAL MALIGNANCIES
 

The immune system in human leukaemia patients seems to be affected both by the disease itself and
by the treatment. The cellular innate immune systems in leukaemia patients differ from healthy
individuals. Monocytes are important cells in the innate immune system, and are today subclassified
into three subpopulations, termed classical, intermediate and non-classical monocytes, based on
their expression of CD14 and CD16. Monocytes have been reported to contribute to haematological
malignancies, for instance, they play an important part in the bone disease, angiogenesis and
immune dysfunction observed in multiple myeloma patients. On the other side, monocytes are
important in combating severe infections in these patients. The role of monocytes in cancer
support, immunoregulation and defence against infections are better characterized in solid tumours
than in haematological malignancies (i.e. liquid tumours). Further studies are needed to elucidate
the monocyte system in patients with haematological malignancies, and the impact of the treatment
against haematological malignancies on circulating monocytes and the monocyte subsets.

Our data show the importance of carefully standardization of sampling and handling when analysing
the distribution of peripheral blood monocytes. For the second part of the project, we have
analysed levels of monocytes and distribution of monocyte subsets in multiple myeloma patients,
receiving autologous stem cell transplantation. We observed a reduction of circulating monocytes
and monocyte subset levels after two days of conditioning therapy, prior patients receiving
autologous stem cell transplantation; this was in contrast to the absolute numbers of leukocytes.
Patients receiving immune modulatory drugs (e.g. Lenalidomide) as part of their treatment showed
lower monocyte levels after conditioning therapy than those who did not. The monocytes and monocyte
subpopulations showed an early regeneration post-autologous stem cell transplantation, which
occurred earlier than normalization of neutrophils and platelets. Our future work will include
elucidating the metabolic response of monocytes to immune modulatory drugs.