cMYC Breakapart - Detail

Translocations involving the cMYC oncogene (Avian Myelocytomatosis Viral Oncogene Homologue) are similar in B-ALL as they are in Burkitt's Lymphoma and result in the close juxtaposition of cMYC to IGH, IGL and IGK in t(8;14)¹, t(8;22) and t(2;8) respectively.

In each case, this results in deregulation of the cMYC (as a result of being close to the constitutively active Immunoglobulin locus), increased transcription and neoplastic growth². The breakpoints involved are widely scattered throughout the gene but the t(8;14) translocation always spares the protein coding exons which become attached to the derived 14. In the t(2;8) and t(8;22) the cMYC remains on chromosome 8 and the Immunoglobulin locus joins it, resulting in the close positioning of the cMYC and Immunoglobulin loci. ALL with these associated translocations (less than 5% of all ALLs) are invariably of the L3 subtype. Most are caused by the t(8;14) (85%), t(8;22) is the next most common at 10% and finally t(2;8) makes up the remaining 5%. Patients with cMYC rearrangements were originally thought to have poor prognoses but they do respond well to intensive chemotherapy affording them an increased survival rate. This shows that cytogenetic confirmation of the rearrangement is necessary to manage the patient effectively³.

References:

1. Moore S et al., Cancer Genet Cytogenet 2003;141:1-4
2. Robertson et al., Nature 1983;302(5908):474-5
3. Hoelzer et al., Blood 1996;87(2):495-508