Expression of the cell cycle regulators p14(ARF) and p16(INK4a) in chronic myeloid leukemia.

Expression of p14(ARF) and p16(INK4a) tumor suppressor genes was investigated in 109 patients with chronic myeloid leukemia (CML). The p14(ARF) and p16(INK4a) mRNA levels were significantly low in patients in chronic phase (CP) at presentation and high in patients treated with interferon-alpha (IFN-alpha), especially in non-responders. A moderate overexpression of p14(ARF) with a normal expression of p16(INK4a) 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-alpha signaling pathway is suggested as well as a relation with the resistance to IFN-alpha or imatinib therapy.