Last update:
16-Oct-2013

Currently cytogenetic analysis at diagnosis provides the most important information about the prognosis of Acute Myeloid Leukemia (AML), with categorization into three distinct prognostic groups (favorable, intermediate and unfavorable). In favorable prognosis AML, specific fusion genes (PML/RARα, AML1/ETO, CBFβ/MYH11) are present. Both conventional cytogenetic analysis and molecular biology techniques contribute to the identification of these genetic lesions. The majority of patients with AML patients belong to the intermediate prognosis group and most of these (about 45% of all cases of AML) carry a normal karyotype at diagnosis, Cytogenetically Normal AML (CN-AML). In recent years, various gene mutations (FLT3, NPM1, CEBPA, MLL, N-RAS, RUNX1, WT-1, IDH) and forms of deregulated gene expression (WT-1, EVI1, PRAME, BAALC, ERG, MN-1) have been identified, illustrating enormous heterogeneity in the CN-AML subset. The prognostic relevance of FLT3 Internal Tandem Duplication (FLT3/ITD), NPM1 mutations and CEBPA biallelic mutations in the CN-AML subset has been documented, and these genetic lesions are currently used for prognostic classification. In studies on patients with t(8;21) AML specific gene mutations (c-KIT, N-RAS, FLT3) have been identified. The c-KIT mutations, identified mainly in exon 8, were found to be associated with an adverse prognosis. Monitoring the Minimal Residual Disease (MRD) after consolidation chemotherapy in patients with AML is important for assessing the risk of relapse. Real time Quantitative Polymerase Chain Reaction (RQ-PCR) analysis has in most instances the sensitivity to detect at least one leukemic cell in 10⁴ background cells. Standardized RQ-PCR procedures have now been developed for the most common types of fusion transcripts (PML/RARα, AML1/ETO and CBFβ/ MYH11) present in AML, allowing large scale MRD studies. In addition, a reliable and highly sensitive RQ-PCR test can be performed in almost 90% of patients with NPM1 mutations (about 35% of all cases of AML, and RQ-PCR assessment of disease level is, through the use of WT-1 overexpression, now feasible in more than 70%.

Key words: AML1/ETO, CBFβ/MYH11, NPM1, PML/RARα, WT-1.