Balkan Journal of Medical Genetics

TWO NOVEL CEBPA MUTATIONS IN A TURKISH PATIENT WITH ACUTE MYELOID LEUKEMIA
Tokgun PE, Alay MT, Atli Tekin S, Güler N, Tokgun O, Demiray A, Karagenc N, Durak T, Celik B, Akca H
*Corresponding Author: Professor Hakan Akca, Department of Medical Genetics, School of Medicine, Pamukkale University, Çamlaraltı, Denizli, Turkey 20070. Tel.: +90-258-296-48-04. Fax: +90-258-296- 17-65. E-mail: hakca@pau.edu.tr
page: 99

INTRODUCTION

Acute myeloid leukemia (AML) is a hematological disorder, was first categorized in 1976, by French, American and British investigators, and divided into eight subgroups (M0 to M7), depending on the cytochemical or histological changes in the leukemic cells. The CEBPA gene, a hematopoietic transcription factor, is located on chromosome 19q13.11, and its prevalence is between 5.0 and 14.0% in AML. The FLT3-ITD, CEBPA and NPM1 genes are the most common mutations that cooperate together in the prognosis of AML. Here, we present two novel pathogenic mutations that create a frameshift mutation on the CEBPA gene, c.940_941insCCGTCGTGG AGACGACGAAGG and c.221_222delAC by Sanger sequencing methodology, described in a 37-year-old woman suffering from menorrhagia, unplanned weight loss in a month and low platelet levels. Acute myeloid leukemia is a hematological disorder, which could be involved in unexpected myeloid stem cell differentiation and proliferation independent from its etiology, without considering a prior hematological disorder or therapy. The World Health Organization (WHO) classified AML by evaluating morphology and immunophenotype in a clinical presentation in 2008, and this was updated in 2016 [1]. In 40.0-50.0% of patients, conventional cyto-genetics and fluorescent in situ hybridization (FISH) methods have failed to detect chromosomal aberrations. Classifying patients in molecularly defined subgroups including CEBPA, FLT3-ITD and NPM1 mutations, are essential for prognosis [2] such as carrying a FLT3-ITD mutation indicates a bad prognosis due to high relapse ratio [3,4], while NPM1 mutations without a FLT3-ITD mutation is indicative of a good prognosis [2,5]. The CCAAT/enhancer binding protein α (C/EBPα) is a hematopoietic transcription factor that is also a member of the basic Zinc finger protein family in 42 and 30 kDA sizes [6,7]. The 42 kDa isoform contains TAD1, TAD2, DNA binding and leucine zipper domain, 30 kDa isoform does not include the TAD1 domain [8]. Prevalence of CEBPA mutations in AML varies between 5.0 and 14.0% [9]. Although CEPBA mutations are commonly biallelic, and the most common type of these mutations includes both N and C terminal regions, their monoallelic forms are rare compared to the biallelic form [2,10]. The N terminal mutations are frameshifts and C terminal mutations are insertions within most common biallelic mutations [9]. Here, we report two new CEBPA mutations, c.940_941insCCG TCGTGGAGACGACGAAGG in the bZIP region and c.221_222delAC in the TAD1 region of the CEBPA protein, which are both frameshift mutations.

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