The cell surface glycoprotein CD47 is a critical “don’t eat me” signal to the innate immune system, which inhibits phagocytosis by binding the signal regulatory protein alpha (SIRPα), an inhibitory immunoreceptor on macrophages. Hematological malignancies, such as AML, express high levels of CD47 as interactions between CD47 on cancer cells and SIRPα on macrophages inhibit phagocytosis resulting, thus, in tumor immune evasion. High expression of CD47 in patients with AML has been associated with poor prognosis, however, there is no standard technique for assessing CD47 expression on AML blasts in clinical practice and the real prognostic value of CD47 overexpression varies among studies in the current literature. The principal aim of this study was to confirm the expression of CD47 on AML blasts and to correlate the levels of CD47 expression to prognosis in order to define the real prognostic value of CD47 overexpression on AML patients. CD47 expression was evaluated by flow cytometry on AML blasts in bone marrow samples performed at diagnosis and reported in terms of 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 HR of 1.04 (CI: 1.01 – 1.08, p 0.047). Further studies with larger sample sizes are necessary to better define the 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.
Sammartano, V. (2024). Prognostic value of CD47 overexpression measured by flow cytometry in patients with acute myeloid leukemia [10.25434/vincenzo-sammartano_phd2024-12-19].
Prognostic value of CD47 overexpression measured by flow cytometry in patients with acute myeloid leukemia
Vincenzo Sammartano
2024-12-19
Abstract
The cell surface glycoprotein CD47 is a critical “don’t eat me” signal to the innate immune system, which inhibits phagocytosis by binding the signal regulatory protein alpha (SIRPα), an inhibitory immunoreceptor on macrophages. Hematological malignancies, such as AML, express high levels of CD47 as interactions between CD47 on cancer cells and SIRPα on macrophages inhibit phagocytosis resulting, thus, in tumor immune evasion. High expression of CD47 in patients with AML has been associated with poor prognosis, however, there is no standard technique for assessing CD47 expression on AML blasts in clinical practice and the real prognostic value of CD47 overexpression varies among studies in the current literature. The principal aim of this study was to confirm the expression of CD47 on AML blasts and to correlate the levels of CD47 expression to prognosis in order to define the real prognostic value of CD47 overexpression on AML patients. CD47 expression was evaluated by flow cytometry on AML blasts in bone marrow samples performed at diagnosis and reported in terms of 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 HR of 1.04 (CI: 1.01 – 1.08, p 0.047). Further studies with larger sample sizes are necessary to better define the 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/1279854