Sleep Disordered Breathing as a Targetable Risk Factor in Multiple Myeloma

ABSTRACT Sleep apnea is a common and underdiagnosed syndrome that impacts at least 4% of American adults and is associated with heart disease, stroke, diabetes, and cancer mortality. In patients with sleep apnea, arterial oxygen saturation intermittently falls. Cyclic episodes are typically followed by rapid re-oxygenation. This cycle occurs as often as 60 times per hour, resulting in chronic intermittent hypoxia (CIH), a dynamic physiology that is distinct from static hypoxia. Our lab is pioneering the study of CIH’s effects on the bone marrow, immunity, and the development of hematological malignancies and we now propose the critical studies necessary to translate our work to human patients. We propose that CIH can cause resistance to chemotherapy by increasing the abundance of tumor-associated macrophages (TAMs). In this proposal, we aim: Aim 1: Test the hypothesis that severity of nighttime chronic intermittent hypoxia promotes TAMs burden Aim 2: Test the hypothesis that continuous positive airway pressure (CPAP) treatment modulates the abundance and gene expression of CD163+ CD206+ macrophages, and Aim 3: Test the hypothesis that chronic intermittent hypoxia decreases the probability of complete remission in newly diagnosed myeloma. By the end of the project period, we will have established that CIH has a clinically meaningful impact on the bone marrow, we will have performed the first deep characterization of TAMs in the context of CIH, and we will have determined the degree to which CIH severity is linked to poor response to chemotherapy.