In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome

• Published in: Blood Vol. 98; no. 9; pp. 2862 - 2864
• Main Authors: Cassinat, Bruno, Chevret, Sylvie, Zassadowski, Fabien, Balitrand, Nicole, Guillemot, Isabelle, Menot, Marie-Laurence, Degos, Laurent, Fenaux, Pierre, Chomienne, Christine
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.11.2001; The Americain Society of Hematology
• Subjects: Adult; Antineoplastic agents; Biological and medical sciences; Bone Marrow Cells - drug effects; Bone Marrow Cells - pathology; Cell Culture Techniques; Cell Differentiation - drug effects; Chemotherapy; Cohort Studies; Drug Resistance; Hematologic and hematopoietic diseases; Humans; Leukemia, Promyelocytic, Acute - drug therapy; Leukemia, Promyelocytic, Acute - mortality; Leukemia, Promyelocytic, Acute - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Middle Aged; Multivariate Analysis; Myeloid Cells - drug effects; Myeloid Cells - pathology; Pharmacology. Drug treatments; Prognosis; Reproducibility of Results; Survival Analysis; Treatment Outcome; Tretinoin - pharmacology; Antineoplastic agent; Human; Relapse; Prognosis; Treatment; Promyelocyte; Retinoid; Cell differentiation; In vitro; Tumor cell; M3 acute myelocytic leukemia; Tretinoin
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.9.2862

Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-transretinoic acid (ATRA). Multicenter trials confirm that the combination of differentiation and cytotoxic therapy prolongs survival in APL patients. However relapses still occur, and exquisite adaptation of therapy to prognostic factors is essential to aim at a possible cure of the disease. A heterogeneity was previously reported in the differentiation rate of patients' APL blasts, and it was postulated that this may reflect the in vivo heterogeneous outcome. In this study, it is demonstrated that patients of the APL93 trial whose leukemic cells achieved optimal differentiation with ATRA in vitro at diagnosis had a significantly improved event-free survival (P = .01) and lower relapse rate (P = .04). This analysis highlights the importance of the differentiation step in APL therapy and justifies ongoing studies aimed at identifying novel RA-differentiation enhancers.