According to Ciro Roberto Rinaldi and collaborating researchers, CD47, but not calreticulin (CALR), was overexpressed on the membrane of patients with myeloproliferative neoplasms (MPS), “suggesting a role for CD47 as a strong antiphagocytic signal responsible for immune survival in MPN.” Among different MPN subtypes, CD47 expression was significantly increased in polycythemia vera (PV) and myelofibrosis (MF), but not essential thrombocythemia (ET).
The study, presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, assessed the expression of CALR and CD47 in treatment-naïve patients with ET, PV, and MF and in healthy controls. The cellular location of CALR and CD47 was also assessed in the membrane, cytoplasm, cytosol, and nucleus.
Reportedly, the total CALR and CD47 protein expression was increased in MPN samples when compared to controls—7.9 vs. 5.1-fold and 2.7 vs 2.2-fold for CALR and CD47, respectively. CD47 demonstrated greater expression of its overall protein on cell membranes when compared to CALR localization (22% vs. 13.9%). All MPN subtypes exhibited a significant reduction of CALR after treatment with cyto-reductive agents. “Interestingly,” noted the authors, “we have observed a significant increase in CD47 cell membrane expression after treatment in MF and PV, suggesting an anti-phagocytic effect induced by cytotoxic drugs.” Conversely, the reduction of CD47 expression in ET cell membranes suggested a prophagocytic effect.
Overall, Rinaldi and colleagues proposed that “the use of anti-CD47 antibodies could represent a new strategy to enhance the treatment response, in particular in PV and MF.”