Expression of the cell cycle regulators p14ARF and p16INK4a in chronic myeloid leukemia

Expression of p14ARF and p16INK4a tumor suppressor genes was investigated in 109 patients with chronic myeloid leukemia (CML). The p14ARF and p16INK4a mRNA levels were significantly low in patients in chronic phase (CP) at presentation and high in patients treated with interferon-α (IFN-α), especially in non-responders. A moderate overexpression of p14ARF with a normal expression of p16INK4a was observed in imatinib-resistant patients. Although protein expression did not consistently match mRNA levels, a role for the two cell cycle regulators in the IFN-α signaling pathway is suggested as well as a relation with the resistance to IFN-α or imatinib therapy.