Inactivation of p14ARF as a key event for the progression of adult T cell leukemia/lymphoma

The INK4a/ARF locus encodes two different proteins, p16INK4a and p14ARF, which are crucial for two tumor suppressor pathways. We found that p14ARF mRNA expression was suppressed in 13 of 37 cases, among which 9 cases showed the inactivation of both of p14ARF and p16INK4a, and 4 cases showed the inactivation of p14ARF alone. The inactivation of p14ARF and the mutation of p53 are mutually exclusive. The patients with the p14ARF inactivation had shorter survival, similar to that of patients with the p53 mutation. These results indicate that the inactivation of p14ARF plays a key role in the progression of ATLL.