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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2862-2864
BRIEF REPORT
In vitro all-trans retinoic acid sensitivity of acute
promyelocytic leukemia blasts: a novel indicator of poor
patient outcome
Bruno Cassinat,
Sylvie Chevret,
Fabien Zassadowski,
Nicole Balitrand,
Isabelle Guillemot,
Marie-Laurence Menot,
Laurent Degos,
Pierre Fenaux, and
Christine Chomienne for the European APL
Group
From the Laboratoire de Biologie Cellulaire
Hématopoïétique, Nuclear Medicine Department, the
Department of Bio-Statistics, and the Hematology Department,
Saint-Louis Hospital, Paris, France, and from the Hematology
Department, Huriet Hospital, Lilles, France.
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.
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