الفهرس 
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Abstract
Acute myeloid leukemia (AML) is a genetically heterogeneous clonal disorder . AML is characterized by the accumulation of acquired somatic genetic alterations in hematopoietic progenitor cells that alter normal mechanisms of self-renewal, proliferation and differentiation. Non-random clonal chromosome aberrations (i.e., balanced translocations, inversions, deletions, monosomies, and trisomies) are detectable in the leukemic blasts of approximately 55% of adults with AML. These chromosomal changes have contributed to the classification of the disease and have been recognized as the most important prognostic factor for achievement of complete remission, risk of relapse, and overall survival (Mrózek et al ., 2004) . A number of gene mutations as well as deregulated expression of genes have been identified, illustrating the enormous heterogeneity of cytogenetically defined AML subsets, in particular in the large subset of AML exhibiting a normal karyotype (Wolff et al .,2007) . The characterization of the gene mutations has provided insights into the mechanisms of leukemogenesis. from a clinical point of view there are two important aspects. First, some of these gene mutations have emerged as important prognostic and predictive markers. Second, novel therapies are now being developed that target these molecular changes. Based on these findings, it is recommended to include molecular genetic diagnosis of several of these markers in the initial work-up of a patient with newly diagnosed AML (Mrózek et al ., 2007) . Nucleophosmin (NPM1) is one of the most abundant proteins in the nucleolus. Despite its nucleolar localization, NPM1 physiologically shuttles constantly across various cell compartments (nucleolus, nucleoplasm, cytoplasm) and This traffic is critical for most of its functions, including regulation of ribosome biogenesis and control of centrosome duplication . NPM1 also interacts with the tumor suppressor ARF and p53, and influences the cellular apoptotic response (Lowenberg , 2008). Somatic mutations in exon 12 of the NPM gene (NPM1) are the most frequent genetic abnormality in adult AML, found in approximately 35% of all cases and up to 60% of patients with normal karyotype AML (Falini et al ., 2005) . NPM1 mutations lead to aberrant localization of the NPM protein into the cytoplasm, thus the designation , NPMc+ AML . NPMc+ AML is seen predominantly in patients with a normal karyotype and is essentially mutually exclusive of recurrent chromosomal translocations. Patients with NPM1 mutations are twice as likely as those who lack an NPM1 mutation to also have an FMS-like tyrosine kinase (FLT3) internal tandem duplication (ITD) mutation (Falini et al ., 2009). NPMc+ AML has important prognostic significance, as NPMc+ AML , in the absence of a coexisting FLT3-ITD mutation, is associated with a favorable outcome. NPM1 mutations have also shown great stability during disease evolution, and therefore represent a possible marker for minimal residual disease detection. Given its distinctive biologic and clinical features and its clear clinical relevance, NPMc+ AML is included as a provisional entity in the 2008 World Health Organization (WHO) classification of AML . There is still much to be learned about this genetic alteration, including its exact role in leukemogenesis , how it interacts with other mutations, and why it confers a more favorable prognosis. Further, it represents a potential therapeutic target warranting research aimed at identifying novel small molecules with activity in NPMc+ AML (Luo et al ., 2010). Aim of the work The aim of the work of this study is to investigate the incidence , prognostic impact of NPM1 mutations on AML patients and study if NPM1 mutations are associated with cytogenetic abnormalities or not.