Prognostic value of CD47 overexpression measured by flow cytometry in acute myeloid leukemia

Abstract

The glycoprotein CD47 is an innate immune checkpoint ubiquitously expressed on all healthy cells to prevent themselves from phagocytosis. CD47 binds to its receptor SIRPα on macrophages, thus producing a signal transduction cascade which inhibits phagocytosis. CD47 is overexpressed on various solid and hematologic malignancies in order to escape the immune system. High expression of CD47 in patients with AML has been associated with poor prognosis, however, there is no standard technique to assess CD47 expression on AML blasts in clinical practice and the real prognostic value of CD47 overexpression varies among studies in the current literature. In this study, CD47 expression was evaluated by flow cytometry on AML blasts from bone marrow samples at diagnosis and reported in terms of median fluorescence intensity (MFI). Flow cytometry analysis demonstrated the expression of CD47 in all AML patients with a median MFI on leukemic blasts of 16.8 (range 2-693.63). CD47 levels on AML blasts correlated with WBC count (rs 0.403, p = 0.016), BM blasts percentage (rs 0.494, p = 0.003), PB blasts percentage (rs 0.482, p = 0.003) and LDH levels (rs 0.382, p = 0.028) and higher expression of CD47 was associated with reduced survival with a hazard ratio of 1.04 (CI: 1.01-1.08, p = 0.047). Further studies with larger sample sizes are necessary to better define the real prognostic value of CD47 overexpression in the complexity of AML tumor microenvironment and, possibly, to identify a subgroup of patients who could derive maximum benefit from emerging CD47-SIRPα blocking therapies.

Keywords: Acute myeloid leukemia; CD47; Tumor microenvironment.

Fig. 1

Identification by flow cytometry of the CD47 expression on AML blasts and the residual normal lymphocytic population