FUNCTIONAL-CHARACTERISTICS OF MATURE GRANULOCYTES IN A PATIENT WITH ACUTE PROMYELOCYTIC LEUKEMIA TREATED WITH ALL-TRANS-RETINOIC ACID

All-trans retinoic acid (ATRA) is a differentiating agent that has bee n successfully used in the treatment of patients with acute promyelocy tic leukemia (APL). Functional properties of peripheral blood neutroph ils from a patient with APL during treatment with ATRA have been studi ed. Wright stain of patient neutrophils showed hypogranulation and loo se nuclear chromatin when compared with normal neutrophils. These cell s were of lower density than normal neutrophils and separated on densi ty gradient centrifugation with mononuclear cells. Surface antigen exp ression by FAGS distinguished these cells from lymphocytes. The histog rams showed a population of larger cells expressing CD18 and CD11b, di stinct from the smaller cells which did not express CD11b, fMLP caused an increase in intracellular calcium (measured spectrophotometrical l y) that was inhibited by the calcium chelator BAPTA. Actin polymerizat ion following cell activation was measured using NBD-phallacidin stain ing and FAGS. Both IL-8 and fMLP caused rapid increases using F-actin content (2.5-3.0 fold), which were of greater magnitude than generally seen with normal neutrophils. Treatment with BAPTA before activation with fMLP did not blunt the actin responses, despite complete inhibiti on of an intracellular calcium increase. In summary, neutrophils deriv ed from differentiated APL cells express CD18/CD11b, and exhibit a sim ilar degree of actin polymerization in response to fMLP and IL-8, inde pendent of an increase in intracellular calcium. Although the actin re sponses are greater than normal neutrophils, most properties are simil ar, supporting the contention that these cells can protect the host. T he exaggerated actin response to inflammatory mediators, however, may play a role in the 'retinoic acid syndrome'.