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Determination of P‐glycoprotein, MDR‐related protein 1, breast cancer resistance protein, and lung‐resistance protein expression in leukemic stem cells of acute myeloid leukemia
Author(s) -
de FigueiredoPontes Lorena L.,
Pintão MariaCarolina T.,
Oliveira Luciana C. O.,
Dalmazzo Leandro F. F.,
Jácomo Rafael H.,
Garcia Aglair B.,
Falcão Roberto P.,
Rego Eduardo M.
Publication year - 2008
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.20403
Subject(s) - cd38 , cd34 , myeloid leukemia , haematopoiesis , stem cell , abcg2 , leukemia , biology , cancer research , p glycoprotein , multiple drug resistance , myeloid , microbiology and biotechnology , immunology , drug resistance , atp binding cassette transporter , biochemistry , transporter , gene
Background: The most primitive leukemic precursor in acute myeloid leukemia (AML) is thought to be the leukemic stem cell (LSC), which retains the properties of self‐renewal and high proliferative capacity and quiescence of the hematopoietic stem cell. LSC seems to be immunophenotypically distinct and more resistant to chemotherapy than the more committed blasts. Considering that the multidrug resistance (MDR) constitutive expression may be a barrier to therapy in AML, we have investigated whether various MDR transporters were differentially expressed at the protein level by different leukemic subsets. Methods: The relative expression of the drug‐efflux pumps P‐gp, MRP, LRP, and BCRP was evaluated by mean fluorescence index (MFI) and the Kolmogorov‐Smirnov analysis ( D values) in five leukemic subpopulations: CD34 + CD38 − CD123 + (LSCs), CD34 + CD38 + CD123 − , CD34 + CD38 + CD123 + , CD34 + CD38 + CD123 − , and CD34 − mature cells in 26 bone marrow samples of CD34 + AML cases. Results: The comparison between the two more immature subsets (LSC versus CD34 + CD38 − CD123 − cells) revealed a higher P‐gp, MRP, and LRP expression in LSCs. The comparative analysis between LSCs and subsets of intermediate maturation (CD34 + CD38 + ) demonstrated the higher BCRP expression in the LSCs. In addition, P‐gp expression was also significantly higher in the LSC compared to CD34 + CD38 + CD123 − subpopulation. Finally, the comparative analysis between LSC and the most mature subset (CD34 − ) revealed higher MRP and LRP and lower P‐gp expression in the LSCs. Conclusions: Considering the cellular heterogeneity of AML, the higher MDR transporters expression at the most immature, self‐renewable, and quiescent LSC population reinforces that MDR is one of the mechanisms responsible for treatment failure. © 2008 Clinical Cytometry Society.