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P-glycoprotein expression in de novo acute myeloid leukemia
G Del Poeta1, A Venditti, G Aronica
1Cattedra e Divisione Ematologia, Universita' Tor Vergata, Roma, Italy.
Abstract:
Detection of the multidrug resistance P-glycoprotein (PGP) phenotype was performed at the time of diagnosis in 223 patients with acute myeloid leukemia (AML) by flow cytometry using C219 Monoclonal Antibody (MoAb). On the other hand, JSB1 MoAb was tested in 173 of these samples. At onset, PGP was detected in 57.4% of cases with C219 and 75.9% of cases with JSB1. There was no correlation between PGP expression and sex, age, marrow blast percentage or extramedullary disease. On the contrary, strict correlations were noted either between C219 negativity and FAB M3 subtype or between C219 positivity and FAB M5 group (P = 0.003). Significant correlation was found between PGP phenotype and CD7, as 143 of 223 samples had similar patterns of staining with C219 (P < 0.0001). Finally, there was a close relationship between C219 and JSB1 positivity: all the C219+ cases were positive for JSB1 (P < 0.0001). Concerning the karyotype, most patients with monosomy or del (7) were MDR positive; on the other hand, most patients with t(8;21) or t(15;17) were MDR negative. Rh123 accumulation studies showed a significant decrease of mean fluorescence intensities both in C219 and in JSB1 positive cases in comparison with PGP negative ones (P < 0.001). A significant decrease of remission induction rates (CR) was highlighted both between C219+ and C219- and between JSB1+ and JSB1- cases (32.1% v 62.1% and 32.6% v 73.8%, respectively, with P < 0.0001). The overall survival and the remission duration (CCR) were significantly shorter both in C219+ and in JSB1+ patients with no relationship to age. Furthermore, a higher rate of early relapses was noted among MDR+ when compared with MDR- patients both for C219+ and JSB1+ cases. The combination (C219- JSB1+) identified a subset of patients with an intermediate prognosis. On multivariate analysis, C219 and JSB1 were confirmed to be independent prognostic factors for achievement of CR, overall survival and CCR. In conclusion, the assessment of MDR phenotype by flow cytometry is a crucial prognostic factor of treatment outcome in AML.
Insights
Multidrug resistance P-glycoprotein (PGP) detection in acute myeloid leukemia (AML) using flow cytometry is a crucial prognostic factor. PGP positivity is linked to poorer remission rates, shorter survival, and increased relapses in AML patients.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Multidrug resistance (MDR) mediated by P-glycoprotein (PGP) is a significant challenge in acute myeloid leukemia (AML) treatment.
- Assessing the PGP phenotype at diagnosis may offer prognostic insights.
Purpose of the Study:
- To evaluate the PGP phenotype in AML patients at diagnosis using flow cytometry.
- To correlate PGP expression with clinical characteristics, cytogenetics, and treatment outcomes.
Main Methods:
- Flow cytometry was used to detect PGP expression with C219 and JSB1 monoclonal antibodies in 223 AML patients.
- Rh123 accumulation studies and correlation with FAB subtypes, CD7 expression, and cytogenetics were performed.
Main Results:
- PGP was detected in a high percentage of AML cases (57.4% with C219, 75.9% with JSB1).
- PGP expression correlated with specific FAB subtypes (M3, M5) and cytogenetic abnormalities (monosomy 7, del(7), t(8;21), t(15;17)).
- PGP-positive patients showed significantly lower complete remission rates (CR), shorter overall survival, and reduced remission duration (CCR).
Conclusions:
- PGP phenotype assessment by flow cytometry is an independent prognostic factor for treatment outcomes in AML.
- MDR status impacts remission induction, survival, and relapse rates, highlighting its clinical significance.