Phagocytosis of terminally differentiated acute promyelocytic leukemia cells by marrow histiocytes during treatment with all-trans retinoic acid

It has been established that acute promyelocytic leukemia (APL) cells are induced to terminally differentiate by all-trans retinoic acid (ATRA), however, the clearance of differentiated APL cells in vivo has not been well understood. Here, we documented the elimination of terminally differentiated APL cells by histiocytes in bone marrow during differentiation induction therapy. In two ATRA-treated APL patients, bone marrow showed the striking phagocytosis of differentiated APL cells by histiocytes just before the achievement of complete remission. Histiocytes phagocytosed APL cells at the terminal stage of differentiation prior to the late apoptotic event of cell lysis. Engulfed APL cells then undergo morphological features of late apoptosis and finally fragmentation in the cytoplasm of histiocytes. This swift and efficient elimination of APL cells undergoing apoptosis by the histiocytes in bone marrow may be possible pathway, at least partially, for the clearance of differentiated APL cells.