MDR1 protein expression is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia.
Little is known about the prognostic role of multidrug resistance (MDR) in adults with newly diagnosed acute lymphoblastic leukemia (ALL). In the context of the GIMEMA ALL0496 protocol, we evaluated the impact of MDR1 (protein expression and function) on the achievement of complete remission (CR) and clinical outcome. Flow cytometric analysis of MDR1 expression (D) and function (rhodamine-123 efflux) was obtained in 203 and 158 patients, respectively. MDR1 expression was detected in 44 (21.7%) of 203 patients, and function was found in 23 (14.6%) of 158 (14.6%) patients. Expression of the multidrug resistance-associated protein 1 (MRP1) and lung-resistance protein (LRP) evaluated in 43 samples was found in 13 and 26 patients, respectively. Among the 200 patients evaluable for the clinical correlation study, 125 (79.6%) of 157 without MDR1 expression achieved CR compared with 23 (53.5%) of 43 with MDR1 expression (P =.001). At univariate analysis, MDR1 expression was significantly associated with CR when considered as a dichotomized (P =.001) or continuous (P =.01) variable. At multivariate analysis, dichotomized evaluation of MDR1 expression independently predicted CR (P =.004) with age (P =.03) and CD34 (P =.03); as a continuous variable, MDR1 expression (P =.03) was the only significant factor other than CD34 (P =.01). MDR1 function failed to predict achievement of CR or of MRP1 and LRP expression. MDR1 expression did not correlate with CR duration, nor did it predict for survival duration. These results demonstrate that MDR1 expression in de novo adult ALL is an independent predictor of CR achievement.
Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, Roma, Italy. agotaf@bce.med.uniroma1.it
Agostino
A
Tafuri
Chiara
C
Gregorj
Maria T
MT
Petrucci
Maria R
MR
Ricciardi
Marco
M
Mancini
Giuseppe
G
Cimino
Cristina
C
Mecucci
Alessandra
A
Tedeschi
Giuseppe
G
Fioritoni
Felicetto
F
Ferrara
Francesco
F
Di Raimondo
Eugenio
E
Gallo
Vincenzo
V
Liso
Francesco
F
Fabbiano
Nicola
N
Cascavilla
Giovanni
G
Pizzolo
Andrea
A
Camera
Fabrizio
F
Pane
Francesco
F
Lanza
Daniela
D
Cilloni
Luciana
L
Annino
Antonella
A
Vitale
Maria L
ML
Vegna
Marco
M
Vignetti
Robin
R
Foà
Franco
F
Mandelli
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D001752:Blast Crisis / Q000473:pathology; D001773:Blood Cells / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015415:Biomarkers