الفهرس 
ACUTE MYELOID LEUKEMIAOnly 14 pages are availabe for public view
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Abstract
A
cute myeloid leukemia (AML) with mutated NPM1 accounts for approximately one-third of all AML cases. Its most distinguishing feature is the aberrant expression of NPM1 in the cytoplasm of leukemic cells. It has distinct genetic, pathologic, immunophenotypic, and clinical characteristics. It is commonly associated with high TLC, acute myelomonocytic and acute monocytic leukemia, CD34 negativity, normal karyotype and favourable prognosis in the absence of FLT-ITD mutation.
The current study aimed to evaluate the efficiency of flow cytometric assay of mutant NPM1 protein in newly diagnosed AML patients and to correlate it with NPM1 gene mutation. Also, the relation between this mutation and clinical, morphological and immunophenotypic data was investigated.
Thirty four newly diagnosed AML patients were evaluated for expression of mutant NPM1 using an antibody specific to it using flow cytometry. Twenty eight patients (out of 34) were evaluated for the presence of NPM1 exon 12 mutations using HRM PCR.
The NPM1 mutation was found in 9 (32.1%) patients by HRM PCR. These patients showed a statistically significant higher level of percentage of positive stained cells (% positive cells) for mutant NPM1 by flow cytometry than the negative mutation group. Using a ROC curve, a cut off value of 27% showing 67% sensitivity and 95% specificity was determined (AUC = 0.772). The MFI of positively stained cells showed no statistically significant difference between the two groups. Taking HRM PCR as reference, flow cytometry results were discrepant in 4 cases (1 false positive and 3 false negative).
In the current study, no significant differences regarding age, gender, splenomegaly, hepatomegaly, lymphadenopathy were observed between NPM1 mutated and un-mutated groups (via HRM PCR). Also disease outcome (number of deaths and patients entering CR, OS and EFS) showed no significant difference between groups.
Regarding laboratory data (TLC, PB blasts %, hemoglobin and platelet count, FAB classification (M4/5), CD34, cytogenetic abnormalities), none of them showed significant difference between positive and negative NPM1 mutation groups; Only one patient with positive NPM1 mutation showed a t(15;17).
In conclusion, our results present flow cytometric detection of mutant NPM1 as a possible test indicating NPM1 mutational status. This tool holds significant potential to be incorporated in the routine acute leukemia panel saving both time and money in resource restricted areas. Eventually, positive samples by flow cytometry are to be validated and further identified by quantitative real-time PCR.