Model of the role of chemokines and dexamethasone in the DS. Schematic representation of the role of chemokines (A) and dexamethasone (B) in the DS. (A) ATRA forces APL blasts to differentiate into mature granulocytes (MGG staining ×400). (1) In addition, ATRA induces chemokine production by the differentiating APL cells (2) as well as by alveolar epithelial cells (3). Alveolar chemokine secretion triggers the migration of differentiating APL cells to the lung (gray arrows). Enhanced migration of leukemic cells in response to massive chemokine production by the differentiating APL cells infiltrating the lung (black arrows) will aggravate the hyperinflammatory reaction in the lung. (B) Reduction of the alveolar chemokine secretion by dexamethasone (DEX) can eliminate the initial trigger for migration of APL cells to the lung and thereby may prevent pulmonary infiltration of APL cells (gray arrows). Dexamethasone does not abrogate the chemokine induction in APL cells. As soon as differentiating APL cells have infiltrated the lung, the ongoing chemokine production by these cells will enhance migration of leukemic cells toward the lung (black arrows), resulting in a severe hyperinflammatory reaction.