Effects of CD47 Expression on Macrophage-Mediated Phagocytosis of Acute Myeloid Leukemia

Kayla Koenig

Document Type

Article

Publication Date

8-9-2024

Keywords

JGM

JAX Location

In: Student Reports, Summer 2024, The Jackson Laboratory

Abstract

Acute Myeloid Leukemia (AML) is a hematological disease caused by the proliferation of immature myeloid precursors in the bone marrow. While chemotherapy remains the first-line treatment approach and exerts anti-tumor effects, this treatment is often less tolerated by older patients and can significantly increase the risk of patient death. This finding has encouraged investigation into the use of immunotherapeutic targets to overcome the obstacles arising from chemotherapies. The cell surface receptor CD47 presents a favorable target due to its role in suppressing phagocytosis and allowing leukemia cells to evade immune detection. CD4 7 has been shown to be upregulated in many cancers, including AML. As therapeutics directly targeting CD47 caused adverse reactions in clinical trials, we investigated upstream regulators and regulatory sites on CD4 7 and assessed the functional consequences of modulations in surface expression. This study was successful in identifying DYRK1A and CBL as positive and negative regulators of CD47, respectively. We found that genetic ablation of these molecules modulated CD47 surface expression, as did elimination of regulatory sites directly on the CD47 protein. These manipulations significantly impacted the progression of macrophage-mediated phagocytosis, providing novel evidence that targeting CD4 7 regulation may present a powerful mechanism by which the CD47-SIRPa axis can be attenuated.

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