Type-A Nucleophosmin (Npm1) Gene Mutation as a Prognostic Marker in Myelodysplastic Syndrome Patients with Normal Karyotypes

Background: MDS are stem cell disorders characterized by impaired hematopoiesis, and variable risk of AML. MDS can be primary or secondary with several risk factors incriminated. Increased apoptosis, genetic aberrations and autoimmune disorders are the key mechanisms incriminated in disease pathogenesis. NPM1, a shuttling protein that has several functions, is a commonly investigated marker in AML. NPM1 gene mutations occur frequently in AML, and are strongly associated with normal karyotypes. Exact molecular factors underlying progress from MDS to secondary AML are largely unknown. Aim of this work: was designed to investigate the prognostic value of nucleophosmin (NPM1) exon 12 mutation type A in adult patients with myelodysplastic syndrome and normal karyotype. Subjects and method: This study included 40 subjects divided into two groups: Patient group, 30 adults with de novo MDS and normal karyotype, their age ranged 17-85 years with a mean±SD 47.70±18.31years. The diagnosis of patients was described according to the revised WHO classification. Accordingly, 12 patients (40.0%) had refractory cytopenia (RC), 9 patients (30.0%) suffering from refactory cytopenia with multilineage dysplasia (RCMD), 4 patients (13.3%) had refractory anemia with excess blast type I(RAEB-I) and 3 patients (10.0%) classified as (RAEB-II) and 2 (6.6%) diagnosed as unclassified MDS (MDS-u). According to International Prognostic Scoring System (IPSS), the patients were classified into low risk (15 patients, 50%), intermediate-1 risk(10 patients, 33.33 %) intermediate- 2 risk (5 patients, 16.66 % ), High risk (0 % ). Control group; 10 apparently healthy adult volunteers of matched age and sex. Age range from 19 to75 with a mean ±SD 43.25±20 years. Results: By using of reverse transcription PCR (RT-PCR), Two (6.6%) patients were positive for a nucleophosmin gene mutation (NPM1- mutA), one case with RAEB-I and one case had RAEB-II. NPM1 mutA was restricted to patients with intermediate risk, while no healthy individual was positive for it. Conclusions; (NPM1-mutA) is a rare finding in adult patients with de novo MDS and normal karyotype, and appears to be restricted to those patients with intermediate risk of progression to AML. None of these patients had a disease that progressed to AML. We concluded that NPM1 mutA may be a favourable early molecular event that confers some protection against evolution of AML, and thus might be a good prognostic factor in AML, but this needs to be confirmed with further Studies on large cohort. (Enas Swelam; Ahmad Baraka; Mohamed H. Murad and Hatem M. Salem. Type-A Nucleophosmin (Npm1) Gene Mutation as a Prognostic Marker in Myelodysplastic Syndrome Patients with Normal Karyotypes. Life Science Journal 2011; 8(4):1159-1165). (ISSN: 1097-8135). http://www.lifesciencesite.com. 142