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Digital Pathology & Pathologists 2016
December 05-06, 2016
Volume 6 Issue 5(Suppl) J Clin Exp Pathol
ISSN: 2161-0681 JCEP, an open access journal
conferenceseries .com
December 05-06, 2016 Madrid, Spain
9th World Digital Pathology & Pathologists Congress
J Clin Exp Pathol 2016, 6:5(Suppl)
Association of MDR1 gene polymorphism (G2677T) with Imatinib response in Egyptian chronic
myeloid leukemia patients
Lamia Ibrahim
Mansoura University, Egypt
Background: Despite the excellent efficacy results of imatinib treatment in CML patients, resistance to imatinib has emerged
as a significant problem. Genetic variations in genes involved in drug transportation might influence the pharmacokinetic and
metabolism of imatinib. The genotype of a patient is increasingly recognized in influencing the response to the treatment. Aim:
To investigate the genotype frequencies of single nucleotide polymorphisms (SNPs) G2677T in CML patients undergoing
imatinib treatment to determine whether different genotype pattern of these SNPs have any influence in mediating response
to imatinib. Methods: A total of 96 CML and 90 control samples were analyzed for the human multidrug resistance gene
1 (MDR1) gene polymorphism (G2677T) using polymerase chain reaction-restriction fragment length polymorphism
technique. Results: Genotype distribution revealed a significant lower frequency of TT genotype in CML patients and non-
significant difference in the GG, GT genotype frequencies between patients and controls (P=0.004, 0.138, 0.210, respectively).
GG genotype was significantly higher in chronic phase (P=0.046), while GT genotype was significantly higher in Blastic
crisis phase (P=0.002). There was a significant difference in genotype frequency of G2677T among patients showing response
and resistance to imatinib in chronic phase (P=0.02). TT genotype was associated with complete hematological response
(P=0.01), complete cytogenetic response (P<0.001), and better molecular response with a significant association (P<0.001). GT
genotype was associated with partial hematological response (P=0.01) and minor cytogenetic response (P<0.001). Optimal and
suboptimal responses were observed for patients with TT genotype (P=0.003). Failure of drug response was associated with
GT genotype (P=0.02); however, GG had no association with drug response. Multivariate analysis considered GT genotype
as independent risk factor for resistance (P=0.037), while TT genotype as protective factor against resistance to imatinib (P=
0.008). Conclusion: Determination of MDR1 polymorphisms (G2677T) might be useful in response prediction to therapy
with imatinib in patients with CML.
Meningioma 1 (MN1) expression: Refined risk stratification in acute myeloid leukemia with normal
cytogenetics (CN-AML)
Lamiaa Ibrahim
Mansoura Medical School, Egypt
Background: Prognostic stratification of cytogenetic normal acute myeloid leukemia (CN-AML) is an area of active research.
Aim: The aim of this study was to determine the prognostic importance of the meningioma 1 (MN1) gene expression levels
in CN-AML. Methods: One hundred patients with CN-AML were diagnosed and MN1 expressions were analyzed using
quantitative real-time polymerase chain reaction. Results: High expressions were detected in 48 (48%) patients (expression
range: 2.35–31.99, mean: 13.9±8.49) in comparison with 52 (52%) patients with low expression (expression range: 0.02–2.3,
mean: 0.68±0.77). The course of the disease in patients with high MN1 expression was unfavorable. Patients with high MN1
expression was associated with significant low complete remission rate (62.5 vs. 8.4%, high vs. low MN1, P=0.001) and high
mortality rate (75% vs. 46.1, P=0.03). AML patients with high MN1 expression tended to be refractory (37.5 vs. 19.2%, P=0.00)
and relapse risk (54.1 vs. 23%, P=0.02). Multivariable analysis confirmed high MN1 expression as an independent risk factor
for disease-free survival and overall survival. Conclusion: MN1 over expression independently predicts bad clinical outcome
in CN-AML patients.