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  • Author: Rodica Tălmaci x
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Daniel Coriu, Dumitru Jardan, Cerasela Jardan, Rodica Tălmaci, Mihaela Dragomir and Anca Coliţă

Abstract

Introduction: Acute myeloid leukemia (AML) is a heterogeneous disease characterized by a late onset (it is rare in children), aggressive phenotype and dismal prognosis especially in patients in the older group (>65 years). For risk stratification of patients standard cytogenetic is used along with molecular techniques for point mutation identification. Here we describe a new method using next generation sequencing for identification of mutation in 5 AML recurrently mutated genes - RUNX1, FLT3, DNMT3A, IDH1 and IDH2. Materials and methods: Samples from 40 patients with normal karyotype AML referred to Fundeni Clinical Institute were sequenced. Primer design was performed using LaserGene Genomics suit. Next generation sequencing was performed on MiSeq (Illumina) and results were analyzed using LaserGene Genomics suit. Results of next generation sequencing were compared to Sanger sequencing. Results: No additional mutations were identified in samples from nine patients presenting FLT3-ITD and/or NPM1 mutations. In 25 out of 31 patients with normal karyotype and no FLT3-ITD and NPM1 mutations, we identified mutations in one of the 5 aforementioned genes. All these mutations identified by next generation sequencing were confirmed using the classical Sanger sequencing. Conclusions: We validated a very useful method for mutation identification in AML patients using next generation sequencing. There are many advantages exhibited by this method: it is more cost efficient and it has a higher sensitivity of mutation detection than Sanger sequencing, it has been described as being quantitative and in our case it allowed risk stratification for most of the normal karyotype AML samples which were FLT3-ITD and NPM1 negative.

Open access

Ana Maria Daraban, Adrian Pavel Trifa, Radu Anghel Popp, Diana Botezatu, Marinela Șerban, Valentina Uscatescu, Rodica Talmaci, Daniel Coriu, Carmen Ginghina and Ruxandra Oana Jurcut

Abstract

Objective: The present case-control study aimed at evaluating the contribution of thrombophilic polymorphisms to acute venous (VTE) as well as arterial thrombotic events (ATE) in a population of young women with few traditional thrombotic factors (CVRF).

Methods: We consecutively enrolled patients under 45 years of age, with less than 3 CVRF, evaluated for VTE or ATE, women and men as a comparator. The control group consisted of healthy young women. A thrombophilia panel and genetic testing for Factor V Leiden (FVL), G20210A Prothrombin and MTHFR polimorphisms were done.

Results: A total of 323 persons were enrolled: 71 women and 121 men with thromboembolic events, and 131 healthy female as controls. Hyperhomocysteinemia was more frequent in ATE (30.4%) than VTE female patients (6.25%), p<0.01. Genetic testing was available in 45 women and 84 men with acute thrombotic events and in all controls. Homozygous FVL was associated with VTE in young women (10.3% vs 0% controls, p<0.01). Prothrombin G20210A polymorphism had the lowest prevalence – 5.4% and only heterozygosity was found. MTHFR C677T heterozygosity showed no significant difference between women patients and controls (62.2 % vs 43.5% respectively, p=0.1). The homozygous status, less frequent (6.6%), was not associated with ATE or VTE. Homozygous MTHFR A1298C was associated with VTE in women (17.2% patients vs 4.5% controls, OR 4.34, p 0.02, CI 1.22-15.3).

Conclusion: In young women with few CVRF, mild hyperhomocysteinemia, homozygosity for FVL and for MTHFR A1298C polymorphisms increase the risk for VTE but not ATE. MTHFR polymorphisms are found with increased frequency in both healthy persons and patients therefore, their significance as an important thrombotic risk modifier remains unclear.