Functional characteristics of mature granulocytes in a patient with acute promyelocytic leukemia treated with all- trans retinoic acid

• Published in: Leukemia research 1995-08, Vol.19 (8), p.505-511
• Main Authors: Sham, Ronald L., Phatak, Pradyumna D., Belanger, Kelly A., Braggins, Caroline, Packman, Charles H.
• Format: Article
• Language: English
• Subjects: actin; Actins - metabolism; Antigens, Surface - metabolism; Antineoplastic agents; Biological and medical sciences; Calcium - metabolism; Cell Adhesion Molecules - metabolism; Cell Size - drug effects; Chemotherapy; granulocyte maturation; Granulocytes - drug effects; Granulocytes - physiology; Humans; Immunophenotyping; In Vitro Techniques; Integrins - metabolism; interleukin-8; Interleukin-8 - pharmacology; L-Selectin; Leukemia; Leukemia, Promyelocytic, Acute - drug therapy; Male; Medical sciences; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Pharmacology. Drug treatments; retinoic acid syndrome; trans-retinoic acid; Tretinoin - therapeutic use
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/0145-2126(95)00001-5

All- trans retinoic acid (ATRA) is a differentiating agent that has been successfully used in the treatment of patients with acute promyelocytic leukemia (APL). Functional properties of peripheral blood neutrophils from a patient with APL during treatment with ATRA have been studied. Wright stain of patient neutrophils showed hypogranulation and loose nuclear chromatin when compared with normal neutrophils. These cells were of lower density than normal neutrophils and separated on density gradient centrifugation with mononuclear cells. Surface antigen expression by FACS distinguished these cells from lymphocytes. The histograms showed a population of larger cells expressing CD18 and CD11b, distinct from the smaller cells which did not express CD11b. fMLP caused an increase in intracellular calcium (measured spectrophotometrically) that was inhibited by the calcium chelator BAPTA. Actin polymerization following cell activation was measured using NBD-phallacidin staining and FACS. 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 inhibition of an intracellular calcium increase. In summary, neutrophils derived from differentiated APL cells express CD18/CD11b, and exhibit a similar degree of actin polymerization in response to fMLP and IL-8, independent of an increase in intracellular calcium. Although the actin responses are greater than normal neutrophils, most properties are similar, supporting the contention that these cells can protect the host. The exaggerated actin response to inflammatory mediators, however, may play a role in the ‘retinoic acid syndrome’.