title: In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome.
abstract: Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-trans retinoic 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.
authors.affiliation: Laboratoire de Biologie Cellulaire Hématopoïétique, Nuclear Medicine Department, Saint-Louis Hospital, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Cassinat
authors.forename: S
authors.initials: S
authors.lastname: Chevret
authors.forename: F
authors.initials: F
authors.lastname: Zassadowski
authors.forename: N
authors.initials: N
authors.lastname: Balitrand
authors.forename: I
authors.initials: I
authors.lastname: Guillemot
authors.forename: M L
authors.initials: ML
authors.lastname: Menot
authors.forename: L
authors.initials: L
authors.lastname: Degos
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
authors.forename: C
authors.initials: C
authors.lastname: Chomienne
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D015331:Cohort Studies; D004351:Drug Resistance; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D022423:Myeloid Cells / Q000187:drug effects / Q000473:pathology; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis; D016896:Treatment Outcome; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D014212:Tretinoin