The role of MDR-related proteins in the prognosis of adult acute myeloid leukaemia (AML) with normal karyotype.
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.
Damiani
Daniela
D
Chair of Hematology and Division of Hematology and Bone Marrow Transplantation, Udine University, Udine, Italy. daniela.damiani@uniud.it
Tiribelli
Mario
M
Raspadori
Donatella
D
Michelutti
Angela
A
Gozzetti
Alessandro
A
Calistri
Elisabetta
E
Candoni
Anna
A
Chiarvesio
Alexsia
A
Lenoci
Mariapia
M
Russo
Domenico
D
Fanin
Renato
R
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
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins