title: The role of MDR-related proteins in the prognosis of adult acute myeloid leukaemia (AML) with normal karyotype.
abstract: Cytogenetic abnormalities are among the most important factors affecting the outcome of patients with acute myeloid leukaemia (AML), but approximately 40-50% of AML cases display a normal karyotype at diagnosis. Multidrug resistance (MDR) proteins overexpression is associated with worse prognosis in acute leukaemias, but its role in normal karyotype AML is less defined. We analysed the expression of P-glycoprotein (PGP), MDR-related protein (MRP) and lung resistance protein (LRP) in 135 adult patients with normal karyotype AML and its correlation with other biological features of the disease, to evaluate the impact of MDR proteins on response to therapy and on survival. Increased PGP expression was associated with lower rate of complete remission (CR; p = 0.006), similarly to advanced age. Cases overexpressing PGP displayed also a shorter event-free survival (EFS; 4 vs. 10 months, p = 0.035) and the increased expression of at least one MDR protein was associated with a reduced overall survival (OS; p = 0.038). Also age was predictive of worse prognosis. Our data confirm the prognostic role of MDR proteins, in particular of PGP, also in AML patients with normal karyotype at diagnosis. This finding could be used to stratify patients with different prognosis and to design risk-adapted therapeutic strategies.
authors.affiliation: Chair of Hematology and Division of Hematology and Bone Marrow Transplantation, Udine University, Udine, Italy. daniela.damiani@uniud.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Damiani
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.forename: Donatella
authors.initials: D
authors.lastname: Raspadori
authors.forename: Angela
authors.initials: A
authors.lastname: Michelutti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Calistri
authors.forename: Anna
authors.initials: A
authors.lastname: Candoni
authors.forename: Alexsia
authors.initials: A
authors.lastname: Chiarvesio
authors.forename: Mariapia
authors.initials: M
authors.lastname: Lenoci
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000032:analysis* / Q000502:physiology; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis; D011379:Prognosis; D012074:Remission Induction
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins