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. Copyright © 2007 John Wiley & Sons, Ltd.

[1]  R. Fanin,et al.  Multicentre phase III trial on fludarabine, cytarabine (Ara‐C), and idarubicin versus idarubicin, Ara‐C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients , 2005, British journal of haematology.

[2]  N. Lee,et al.  Multidrug Resistance as a Potential Prognostic Indicator in Acute Myeloid Leukemia with Normal Karyotypes , 2005, Acta Haematologica.

[3]  M. Fey,et al.  Risk Assessment in Patients with Acute Myeloid Leukemia and a Normal Karyotype , 2005, Clinical Cancer Research.

[4]  C. Bloomfield,et al.  Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: a cancer and leukemia group B study. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Paola Fazi,et al.  Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. , 2005, The New England journal of medicine.

[6]  C. Bloomfield,et al.  Cytogenetics in acute leukemia. , 2004, Blood reviews.

[7]  E. Estey,et al.  FLT3 mutation and response to intensive chemotherapy in young adult and elderly patients with normal karyotype. , 2004, Leukemia research.

[8]  O. Legrand,et al.  P-glycoprotein and multidrug resistance associated protein-1 activity in 132 acute myeloid leukemias according to FAB subtypes and cytogenetics risk groups. , 2004, Haematologica.

[9]  M. Caligiuri,et al.  BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: a Cancer and Leukemia Group B Study. , 2003, Blood.

[10]  J. Bourhis,et al.  Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. , 2003, Blood.

[11]  Axel Benner,et al.  Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. , 2002, Blood.

[12]  S. Seeber,et al.  Impact of the expression of P glycoprotein, the multidrug resistance-related protein, bcl-2, mutant p53, and heat shock protein 27 on response to induction therapy and long-term survival in patients with de novo acute myeloid leukemia. , 2002, Experimental hematology.

[13]  G. Ehninger,et al.  Association of specific cytogenetic aberrations with mdr1 gene expression in adult myeloid leukemia and its implication in treatment outcome. , 2002, Haematologica.

[14]  R. Fanin,et al.  CD56 and PGP expression in acute myeloid leukemia: impact on clinical outcome. , 2002, Haematologica.

[15]  M. Slovak,et al.  Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study , 2000 .

[16]  M. Grever,et al.  Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. , 1999, Blood.

[17]  M. Baccarani,et al.  P‐glycoprotein, lung resistance‐related protein and multidrug resistance associated protein in de novo acute non‐lymphocytic leukaemias: biological and clinical implications , 1999, British journal of haematology.

[18]  K Wheatley,et al.  The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. , 1998, Blood.

[19]  C. Bloomfield,et al.  Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype. , 1998, Cancer research.

[20]  F. Mandelli,et al.  Therapy of acute myeloid leukemia: towards a patient-oriented, risk-adapted approach. , 1998, Haematologica.

[21]  C. Bloomfield,et al.  Long‐term survival of patients with acute myeloid leukemia , 1997, Cancer.

[22]  T. Grogan,et al.  Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia. , 1996, Blood.

[23]  M. Tribalto,et al.  Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia. , 1996, Blood.

[24]  Iscn International System for Human Cytogenetic Nomenclature , 1978 .

[25]  H. Gralnick,et al.  Proposals for the Classification of the Acute Leukaemias French‐American‐British (FAB) Co‐operative Group , 1976, British journal of haematology.