Contributions
Abstract: PB1716
Type: Publication Only
Background
Actual prognostic factors for testing acute leukemia are formed on detectable cytogenetic and molecular-genetic disorders, as well as initial data including the patient's age, leukocytosis, amount blast in the bone marrow. However, the study of genes of primary drugresistance or factors contributing to its development is not mandatory. Expression of the MDR1 gene by tumor cells is considered as one of the most common mechanisms of drugresistance.
Aims
The aim of this study was to assess the risk of developing drugresistance with acute leukemia patients based on MDR1 gene expression determination prior to initiation of therapy.
Methods
The study included 12 patients with acute lymphoblastic leukemia (ALL) and 25 patients with acute myeloblastic leukemia (AML). The average age of the patients was 47.9 ± 15.7 years. Leukemia cells were taken from peripheral blood and bone marrow of patients. Assessment of multidrug resistance in tumor cells of leukemia patients was performed on bone marrow and/or peripheral blood samples using quantitative real-time reverse transcription-polymerase chain reaction (real-time RT-qPCR). RT-qPCR was used to evaluate the expression of the MDR1 gene. The results were normalized to GAPDH used as an internal standard.
All statistical analyses were done with computer software MS Excel, OriginPro 7.5, Statistica 10.0.
Results
All leukemia patients were divided into groups with low, medium and high levels of expression based on the level of expression of MDR1. All leukemia patients were divided into groups based on their response to chemotherapy treatment (effectiveness of chemotherapy). For examination of the chemotherapy effectiveness for acute leukemia patients was determined the number of blasts in the bone marrow after 1-2 chemotherapy courses. The intensive the expression level of the MDR1 gene is, the higher the risk of developing drugresistance is. Patients with AML have a moderate direct correlation (r = 0.66, p <0.05) between the response to therapy and the expression of the MDR1 gene. In patients with ALL, a strong direct correlation was found (r = 0.77, p <0.05) between response to therapy and expression of the MDR1 gene. Thus, patients with expressed expression of this gene should be classified as high risk, low level of expression and its absence - to a low risk group, and with moderate expression - to an intermediate risk group. In patients with high and moderate expression of the MDR1 gene, individual sensitivity to cytostatic drugs should be assessed for personalized correction of therapy regimens.
Conclusion
The data obtained demonstrate the importance of studying the expression level of the MDR1 gene with acute leukemia patients before initiating therapy to assess the prognosis of the disease.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): MDR1, Resistance, acute leukemia, Acute Myeloid Leukemia
Abstract: PB1716
Type: Publication Only
Background
Actual prognostic factors for testing acute leukemia are formed on detectable cytogenetic and molecular-genetic disorders, as well as initial data including the patient's age, leukocytosis, amount blast in the bone marrow. However, the study of genes of primary drugresistance or factors contributing to its development is not mandatory. Expression of the MDR1 gene by tumor cells is considered as one of the most common mechanisms of drugresistance.
Aims
The aim of this study was to assess the risk of developing drugresistance with acute leukemia patients based on MDR1 gene expression determination prior to initiation of therapy.
Methods
The study included 12 patients with acute lymphoblastic leukemia (ALL) and 25 patients with acute myeloblastic leukemia (AML). The average age of the patients was 47.9 ± 15.7 years. Leukemia cells were taken from peripheral blood and bone marrow of patients. Assessment of multidrug resistance in tumor cells of leukemia patients was performed on bone marrow and/or peripheral blood samples using quantitative real-time reverse transcription-polymerase chain reaction (real-time RT-qPCR). RT-qPCR was used to evaluate the expression of the MDR1 gene. The results were normalized to GAPDH used as an internal standard.
All statistical analyses were done with computer software MS Excel, OriginPro 7.5, Statistica 10.0.
Results
All leukemia patients were divided into groups with low, medium and high levels of expression based on the level of expression of MDR1. All leukemia patients were divided into groups based on their response to chemotherapy treatment (effectiveness of chemotherapy). For examination of the chemotherapy effectiveness for acute leukemia patients was determined the number of blasts in the bone marrow after 1-2 chemotherapy courses. The intensive the expression level of the MDR1 gene is, the higher the risk of developing drugresistance is. Patients with AML have a moderate direct correlation (r = 0.66, p <0.05) between the response to therapy and the expression of the MDR1 gene. In patients with ALL, a strong direct correlation was found (r = 0.77, p <0.05) between response to therapy and expression of the MDR1 gene. Thus, patients with expressed expression of this gene should be classified as high risk, low level of expression and its absence - to a low risk group, and with moderate expression - to an intermediate risk group. In patients with high and moderate expression of the MDR1 gene, individual sensitivity to cytostatic drugs should be assessed for personalized correction of therapy regimens.
Conclusion
The data obtained demonstrate the importance of studying the expression level of the MDR1 gene with acute leukemia patients before initiating therapy to assess the prognosis of the disease.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): MDR1, Resistance, acute leukemia, Acute Myeloid Leukemia