Acute lymphoblastic leukemia patients after being treated with methotrexate, have differences in methotrexate serum levels and toxic side effects. One of the main determinants of these toxic side effects is the host pharmacogenetics. The aim of this study was to evaluate the association of -24CT, 1249GA, and 3972CT ABCC2 gene polymorphisms with serum levels, and toxic side effects of methotrexate in childhood acute lymphoblastic leukemia. Applying polymerase chain reaction and restriction fragment length polymorphism techniques, the prevalence of -24CT, 1249GA, and 3972CT ABCC2 gene polymorphisms was evaluated in 65 acute lymphoblastic leukemia patients. The relationship between polymorphisms and methotrexate serum levels and toxicities was studied. A reverse significant relationship was detected between 3972T allele carriers and hepatotoxicity (P = 0.01, OR = 0.25, 95% CI = 0.09-0.72). Also, 1249A allele carriers had increased rate of gastrointestinal toxicity (P = 0.05, OR = 3.47, 95% CI = 1.04-11.57). No significant relationship was detected between -24CT polymorphism and methotrexate toxic side effects. There was no significant relationship between these three polymorphisms and methotrexate serum levels. Genotyping for 3972CT and 1249GA ABCC2 gene variants maybe useful in acute lymphoblastic leukemia to optimize methotrexate therapy and reducing the associated toxicity.
Diagnosis of inherited platelet glycoprotein disorders is based on specific laboratory techniques such as aggregometry and flow cytometry. Flowcytometry is a powerful method, but equivocal results are produced in some cases. New cluster of differentiation markers could resolve the diagnostic dilemmas. Abnormal expression of CD9 in Bernard-Soulier syndrome (BSS) is recently reported. We aimed to determine the diagnostic significance of CD9 expression in a cohort of Iranian patients with inherited platelet glycoprotein defects. Twelve BSS, 21 Glanzmann thrombasthenia and 16 healthy controls were included in the present study. Flowcytometric diagnosis of BSS and Glanzmann thrombasthenia was made by analysis of CD41/61 and CD42a/42b CD markers. Moreover, phycoerythrin-labelled anti CD9 was examined in patients and healthy controls. The mean fluorescence intensity (MFI) of CD9 among the three groups was compared using suitable statistical methods and a P value of less than 0.05 considered statistically significant. Mean MFI of CD9 was 990.0 in BSS patients versus 421.2 and 317.3 in individuals with Glanzmann thrombasthenia and healthy controls, respectively (P < 0.05). Between the two-group comparison of means by the Mann-Whitney test revealed a P value of less than 0.001 for BSS group versus GT (2.4-fold) and BSS versus healthy controls (2.9-fold). CD9 molecule also expressed differently in patients with Glanzmann thrombasthenia in comparison with healthy controls (P < 0.001), although with a less magnitude (1.3-fold). According to our findings, CD9 is a potential biomarker for laboratory diagnosis of inherited glycoprotein defects, especially to elucidate the ambiguous results in BSS cases.
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