Amplification of c-MYC and MLL Genes as a Marker of Clonal Cell Progression in Patients with Myeloid Malignancy and Trisomy of Chromosomes 8 or 11

Abstract

Gene amplification (amp) is one of the basic mechanisms connected with overexpression of oncogenes. The c-MYC (located in 8q24) and MLL (located in 11q23) are the most often over represented genes that lead to a rapid proliferation of the affected cell clone in patients with myeloid neoplasms. Assessment of the level of amp c-MYC or amp MLL in the cases with trisomy 8 (+8) or trisomy 11 (+11) and myeloid malignances is necessary for a more precise estimation of the disease progression.A total of 26 patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) were included in the study: 18 with +8, six with +11 and two with complex karyotypes suspected of the partial trisomy. Routine cytogenetic analysis and fluorescent in situ hybridization (FISH) were applied to indicate the chromosome alterations and genes amp in the bone marrow cells.Amp c-MYC was observed in 12 from 18 (66.7%) patients with +8. All the patients with +11 demonstrated a different level of amp MLL. In most of the cases with MDS (9/10), the coincidence of the +8 or +11 with amp c-MYC or amp MLL, respectively, leads to transformation to AML and/or short overall survival. Our data suggest that amp c-MYC and amp MLL develop in conformity with +8 and +11, especially in cases with progressive deviations in the karyotype as an aggressive expansion of an aberrant cell clone and appearance of additional chromosome anomalies.