Immunophenotyping of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a disease caused by an accumulation of immature myeloid cells, also called blasts, in the bone marrow. It is often clonally heterogeneous. These genetically and functionally distinct subclones can be identified based on their immunophenotype. A panel of 36 plasma membrane markers was composed, of which five were included in the routine diagnostics panel of the UMCG to collect (longitudinal) patient data. By analysing the data from this patient cohort we found that positivity for one or more of the five markers at a specific follow-up time point was predictive for a worse relapse-free survival. An analysis pipeline called CombiFlow was created, which enabled the identification of potential subclones and allowed tracking of disease progression in longitudinal data. Based on their immunophenotype, AML samples could be divided into a more stem cell-like or a more differentiated group. The stem cell-like AML samples were less dependent on specific amino acids and had a lower translation rate. Lastly, one of the markers, CD200, was studied in more detail as knockdown of CD200 reduced proliferation of AML cell lines in vitro and in vivo. High CD200 expression may contribute to stemness through cell intrinsic signalling and by enabling mitochondrial transfer from immune cells in the microenvironment