Coexpression of p53 protein and MDR functional phenotype in leukemias: the predominant association in chronic myeloid leukemia.
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.
Cavalcanti
Geraldo Barroso
GB
Laboratório de Hematologia Celular e Molecular, Serviço de Hematologia, Hospital do Câncer I, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.
Vasconcelos
Flavia da Cunha
FC
Pinto de Faria
Giselle
G
Scheiner
Marcos Antônio Maurício
MA
de Almeida Dobbin
Jane
J
Klumb
Claudete Esteves
CE
Maia
Raquel C
RC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D001752:Blast Crisis; D001854:Bone Marrow Cells; D018432:Drug Resistance, Multiple; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000494:pharmacology; D019450:Genes, MDR; D006801:Humans; D020014:K562 Cells; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D012008:Recurrence; D020112:Rhodamine 123 / Q000494:pharmacology; D013577:Syndrome; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005456:Fluorescent Dyes; D016159:Tumor Suppressor Protein p53; D020112:Rhodamine 123