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Coexpression of p53 protein and MDR functional phenotype in leukemias: The predominant association in chronic myeloid leukemia
Author(s) -
Cavalcanti Geraldo Barroso,
Vasconcelos Flavia da Cunha,
de Faria Giselle Pinto,
Scheiner Marcos Antônio Maurício,
Dobbin Jane de Almeida,
Klumb Claudete Esteves,
Maia Raquel C.
Publication year - 2004
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.20013
Subject(s) - myeloid leukemia , phenotype , flow cytometry , leukemia , cancer research , biology , multiple drug resistance , chronic lymphocytic leukemia , myeloid , p glycoprotein , immunology , rhodamine 123 , drug resistance , gene , genetics
Background One of the best characterized resistance mechanisms of leukemias is multidrug resistance (MDR) mediated by P‐glycoprotein (Pgp) and multidrug‐resistant related protein (MRP). In addition to Pgp and MRP, p53 mutation or inactivation might play a relevant role in therapeutic failure. Some studies have demonstrated that Pgp and MRP may be activated in association with overexpression of mutant or inactivated p53 protein. The aim of this study was to investigate the association between p53 expression and MDR functional phenotype analyzed by flow cytometry (FCM). Methods Rhodamine‐123 assay analyzed by FCM was used to detect the MDR phenotype that was positive in 18 out of 41 (43.9%) cases of chronic myeloid leukemia (CML), 16 out of 28 (57.1%) chronic lymphoid leukemia (CLL) cases, 11 out of 28 (39.3%) acute myeloid leukemia (AML) cases, and four out of 22 (18.2%) acute lymphoid leukemia (ALL) cases. Results Variable levels of p53 expression were observed in leukemic cells: 12 out of 41 (29.2%) in CML, nine out of 28 (32.1%) in CLL, 15 out of 28 (53.6%) in AML, and eight out of 22 (36.4%) in ALL samples. Conclusions In our study, no significant association between p53 expression and MDR functional phenotype was observed in ALL, CLL, and AML. On the other hand, a significant association ( P = 0.0003) of the coexpression was observed in CML. The p53 overexpression was more frequently seen in the accelerated phase and the blastic phase of this disease. Our results suggest that an MDR functional phenotype could be associated with p53 mutation in the advanced stage of leukemias. © 2004 Wiley‐Liss, Inc.