ABCB1 and BMI1 mRNA expression in patients with chronic myeloid leukemia: impact on imatinib efficacy

Ahmed M. L. Bedewy,Shereen M. Elmaghraby,Noha S. Kandil 대한혈액학회 2019 Blood Research Vol.54 No.1

BackgroundATP-binding cassette transporters are important in the mechanism of multidrug resistance. ABCB1 displays a high affinity for imatinib. BMI1 is a polycomb group protein thought to be overexpressed in leukemic cells.MethodsThis study was conducted to investigate the prognostic value of ABCB1 and BMI1 ex-pressions in chronic myeloid leukemia (CML). Expression levels were measured in 81 patients newly diagnosed with CML and 20 healthy controls by real time reverse tran-scription-PCR. ResultsThe ABCB1 expression levels did not differ between patients with CML and controls. Low ABCB1 mRNA levels were observed in patients who achieved an optimal response com-pared to suboptimal and resistant cases (P=0.005). Non-responders showed the highest ABCB1 levels. ABCB1 expression did not affect the progression-free survival (PFS) of patients. BMI1 expression was higher in patients than that in controls (P=0.001). Patients in advanced phases expressed higher levels of BMI1 than those in the chronic phase (P=0.004). High BMI1 expression was associated with a shorter PFS.ConclusionABCB1 mRNA expression may serve as a predictor of the optimal response to imatinib treatment in patients with CML. BMI1 expression was higher in the accelerated and blastic crisis phases of CML and associated with a shorter PFS.

The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia

Ahmed M. L. Bedewy,Shereen M. EL-Maghraby,Noha S. Kandil,Waleed R. El-Bendary 대한혈액학회 2015 Blood Research Vol.50 No.4

BackgroundTherapeutic protocols used in adult acute lymphoblastic leukemia (ALL) are widely varia-ble, and glucocorticoids (GCs) are essential components in ALL treatment. Therefore, this study aimed to evaluate the distribution of prominent glucocorticoid receptor (GR) gene polymorphic variants among adult ALL patients. We also investigated the association be-tween GR messenger ribonucleic acid (mRNA) isoform expressions and the response to chemotherapy.MethodsFifty-two newly diagnosed Philadelphia-negative adult ALL patients and 30 healthy control subjects were enrolled in this study. Genotyping was carried out using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. GR mRNA isoform ex-pressions were assayed by quantitative real-time PCR.ResultsALL patients in this study had a median age of 34 years (range, 18‒75). GR expression was associated with complete remission (P=0.03), while GR mRNA expression was sig-nificantly higher in GC resistant patients (P=0.032) and in non-responders (P=0.019). However, there were no significant associations with GC resistance. The BclI polymorphic variant of the GR gene was the most frequent in adult ALL patients and was not associated with the GC response. Both higher GR expression and lower GR expression were asso-ciated with achievement of complete remission, while higher GR expression was asso-ciated with GC-resistance.ConclusionOur data suggest that the level of GR isoform expression may be useful in predicting GC response, achievement of complete remission, and better event-free survival in ALL patients. However, further evaluation with a larger cohort of patients is warranted.

ABCB1 and BMI1 mRNA expression in patients with chronic myeloid leukemia: impact on imatinib efficacy

Ahmed M. L. Bedewy,Shereen M. Elmaghraby,Noha S. Kandil 대한혈액학회 2019 Blood Research Vol.54 No.1

BackgroundATP-binding cassette transporters are important in the mechanism of multidrug resistance. ABCB1 displays a high affinity for imatinib. BMI1 is a polycomb group protein thought to be overexpressed in leukemic cells.MethodsThis study was conducted to investigate the prognostic value of ABCB1 and BMI1 ex-pressions in chronic myeloid leukemia (CML). Expression levels were measured in 81 patients newly diagnosed with CML and 20 healthy controls by real time reverse tran-scription-PCR. ResultsThe ABCB1 expression levels did not differ between patients with CML and controls. Low ABCB1 mRNA levels were observed in patients who achieved an optimal response com-pared to suboptimal and resistant cases (P=0.005). Non-responders showed the highest ABCB1 levels. ABCB1 expression did not affect the progression-free survival (PFS) of patients. BMI1 expression was higher in patients than that in controls (P=0.001). Patients in advanced phases expressed higher levels of BMI1 than those in the chronic phase (P=0.004). High BMI1 expression was associated with a shorter PFS.ConclusionABCB1 mRNA expression may serve as a predictor of the optimal response to imatinib treatment in patients with CML. BMI1 expression was higher in the accelerated and blastic crisis phases of CML and associated with a shorter PFS.

The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia

Ahmed M. L. Bedewy,Shereen M. EL-Maghraby,Noha S. Kandil,Waleed R. El-Bendary 대한혈액학회 2015 Blood Research Vol.50 No.4

BackgroundTherapeutic protocols used in adult acute lymphoblastic leukemia (ALL) are widely varia-ble, and glucocorticoids (GCs) are essential components in ALL treatment. Therefore, this study aimed to evaluate the distribution of prominent glucocorticoid receptor (GR) gene polymorphic variants among adult ALL patients. We also investigated the association be-tween GR messenger ribonucleic acid (mRNA) isoform expressions and the response to chemotherapy.MethodsFifty-two newly diagnosed Philadelphia-negative adult ALL patients and 30 healthy control subjects were enrolled in this study. Genotyping was carried out using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. GR mRNA isoform ex-pressions were assayed by quantitative real-time PCR.ResultsALL patients in this study had a median age of 34 years (range, 18‒75). GR expression was associated with complete remission (P=0.03), while GR mRNA expression was sig-nificantly higher in GC resistant patients (P=0.032) and in non-responders (P=0.019). However, there were no significant associations with GC resistance. The BclI polymorphic variant of the GR gene was the most frequent in adult ALL patients and was not associated with the GC response. Both higher GR expression and lower GR expression were asso-ciated with achievement of complete remission, while higher GR expression was asso-ciated with GC-resistance.ConclusionOur data suggest that the level of GR isoform expression may be useful in predicting GC response, achievement of complete remission, and better event-free survival in ALL patients. However, further evaluation with a larger cohort of patients is warranted.

CD163 and c-Met expression in the lymph node and the correlations between elevated levels of serum free light chain and the different clinicopathological parameters of advanced classical Hodgkin’s lymphoma

Magdy Bedewy,Shereen El-Maghraby,Ahmed Bedewy 대한혈액학회 2013 Blood Research Vol.48 No.2

Background Advances in the understanding of Hodgkin’s lymphoma (HL) show various functions of infiltrating immune cells and cytokines in relation to clinical outcomes. The expression of CD163 and c-Met has been suggested to have a role in lymphoid malignancy. Thus, we evaluated the expressions of CD163, c-Met, and serum free light chain (sFLC) in relation to the clinicopathological features of patients with advanced classical HL (cHL). Methods We assessed the expression of CD163 and c-Met in 34 patients with cHL through immunohistochemistry on the lymph node biopsy sections and the levels of pretreatment sFLC were estimated using ELISA. Results High CD163 expression correlated with increased age, B symptoms, International Prognostic Score (IPS) ≥3, mixed cellularity subtype, and low response to treatment. Further, high c-Met expression correlated with increased age at diagnosis, leukocytosis, B symptoms, and lower chance to achieve complete remission. The sFLC levels correlated with increased age at diagnosis, lymphopenia, IPS ≥3, B symptoms, and lower complete remission rates. Conclusion In advanced cHL, increased expression of CD163 and c-Met showed a significant association with adverse prognostic parameters and poor response to treatment. Pretreatment high sFLC level also correlated with poor risk factors, suggesting its use as a candidate prognostic marker. A comprehensive approach for prognostic markers might represent a step towards developing a tailored therapeutic approach for HL.

CD163 and c-Met expression in the lymph node and the correlations between elevated levels of serum free light chain and the different clinicopathological parameters of advanced classical Hodgkin’s lymphoma

Magdy Bedewy,Shereen El-Maghraby,Ahmed Bedewy 대한혈액학회 2013 Blood Research Vol.48 No.2

Background Advances in the understanding of Hodgkin’s lymphoma (HL) show various functions of infiltrating immune cells and cytokines in relation to clinical outcomes. The expression of CD163 and c-Met has been suggested to have a role in lymphoid malignancy. Thus, we evaluated the expressions of CD163, c-Met, and serum free light chain (sFLC) in relation to the clinicopathological features of patients with advanced classical HL (cHL). Methods We assessed the expression of CD163 and c-Met in 34 patients with cHL through immunohistochemistry on the lymph node biopsy sections and the levels of pretreatment sFLC were estimated using ELISA. Results High CD163 expression correlated with increased age, B symptoms, International Prognostic Score (IPS) ≥3, mixed cellularity subtype, and low response to treatment. Further, high c-Met expression correlated with increased age at diagnosis, leukocytosis, B symptoms, and lower chance to achieve complete remission. The sFLC levels correlated with increased age at diagnosis, lymphopenia, IPS ≥3, B symptoms, and lower complete remission rates. Conclusion In advanced cHL, increased expression of CD163 and c-Met showed a significant association with adverse prognostic parameters and poor response to treatment. Pretreatment high sFLC level also correlated with poor risk factors, suggesting its use as a candidate prognostic marker. A comprehensive approach for prognostic markers might represent a step towards developing a tailored therapeutic approach for HL.