Amplification of the G allele at SNP rs6983267 in 8q24 amplicons in myeloid malignancies as cause of the lack of MYC overexpression?

DNA amplification is a molecular mechanism underlying oncogen- esis, in that amplified genes are often overexpressed consequent to copy number gain [1]. However, some amplified oncogenes display an unexpected lack of overexpression. One example is the 8q24 am- plified region within double minute (dmin) chromosomes in myelo- dysplastic syndromes (MDS) and acute myeloid leukemia (AML) [2] that contains MYC and other genes (TRIB1, FAM84B, POU5F1B, PVT1, and TMEM75). Northern Blotting gene expression analysis revealed that MYC is not upregulated and that TRIB1 is overexpressed in only a subset of such AML cases [2], in marked contrast with the MYC over- expression seen in other neoplasms with MYC amplification [3]. The 8q24 region is also amplified in chronic myeloid leukemia (CML) [4,5]. Here, we investigated by FISH whether the 8q24 amplified region overlaps in AML/MDS and CML. In addition, we measured the expres- sion level of amplified genes in AML/MDS and CML cell lines. Particu- larly, we focused on the MYC gene, aiming to unravel the molecular mechanism(s) behind the observed lack of overexpression when am- plified in leukemias.