Fig. 5: Pharmacologic MERTK blockade inhibits multiple myeloma tumor progression and bone disease.

a–k After intraosseous femoral injection of U266 myeloma cell line, NSG mice were treated with vehicle or 60 mg/kg R992 BID. a Assessment of Igλ light chain paraprotein in the peripheral blood by ELISA (week 3 n = 8/6, week 5 n = 5/4, and week 8 n = 5/5). b Bone marrow CD138⁺ myeloma plasma cell infiltration in the contralateral leg by FACS (n = 5/4). c μCT analysis of bone loss by calculating the change in bone volume (BV/TV) in relation to healthy control mice (n = 7/8). d 3D reconstructions of microcomputed tomography (μCT) recordings of the metaphyseal proximal region of the femur of healthy and myeloma-bearing mice. e Representative pictures of TRAP Hematoxylin staining (osteoclasts stained in red) showing myeloma infiltration in the bone marrow (#1), osteoblasts visible as cuboidal or polygonal mononuclear cells on the endosteal bone surface (arrows in green) (#2), osteolysis (#3), histologically detectable signs of bone repair in osteolysis zones induced by R992 (arrows in green pointing to osteoblasts, arrows in red pointing to osteoclasts) (#4), and detection of TRAP-positive mononuclear cells indicating osteoclast precursor cell recruitment (#5) (arrows in yellow) (n = 5). f Histomorphometric analysis of osteoblast number per bone perimeter (n = 7/8). g Determination of serum bone formation marker P1NP by ELISA (n = 8/8). h Histomorphometric analysis of osteoclast number per bone perimeter. i Determination of serum osteoclast marker TRAP5b by ELISA (n = 8/8). j Histomorphometric analysis of the number of TRAP⁺ mononuclear cells in the bone marrow (n = 7/8). k Kaplan–Meier curve showing overall survival (n = 13/13, p = 0.030 Mantel–Cox test). Median survival was 73 vs. 88 days. Data were means ± SEM. Statistical significance was determined by a two-tailed unpaired t-test unless otherwise stated.