Correlation of hypoxia in MM cells with their egress into the circulation. (A-B) Correlation between the number of circulating MM cells detected by flow cytometry and tumor progression in SCID-MM1s model detected by BLI in the disseminated xenograft model (A) and in the 5T33MM model (B). Results show increased numbers of circulating MM cells mainly in the late stages of tumor progression. (C) Correlation between the number of circulating cells and the level of hypoxia in MM cells in the BM indicated as MFI of PIM, which shows a direct linear correlation. (D) Correlation between hypoxia levels in circulating MM cells and hypoxia in MM cells in the BM from mice with different tumor burdens, which shows that circulating MM cells were hypoxic, with no correlation with the hypoxia in the BM.