Overexpression of p16INK4A and p14ARF in haematological malignancies

Two proteins, p16(INK4A) and p14(ARF) , originating from the same gene locus CDKN2A , use different promoters and alternative reading frames. p16(INK4A) is translated from alpha transcript and p14(ARF) is from beta transcript. These two proteins, which are inactivated in some human malignancies, are possible tumour suppressor candidates. In this study, we investigated the expression of p16(INK4A) and p14(ARF) mRNAs in haematological malignancies. We studied eight normal bone marrow samples, three reactive granulocytic hyperplasia patients, and 21 haematological malignancy patients, including seven acute myelogenous leukaemia, four acute lymphoblastic leukaemia, five myelodysplastic syndrome, five chronic myelogenous leukaemia (CML). p16(INK4A) and p14(ARF) mRNA expression was assayed by reverse transcriptase polymerase chain reaction. Normal bone marrows and reactive granulocytic hyperplasia showed barely detectable expression of either mRNA. In contrast, p16(INK4A) and p14(ARF) mRNA expression was abnormally increased in patients with haematological malignancies. Especially in CML, overexpression of p16(INK4A) and p14(ARF) mRNAs was more frequent than in controls (80 and 60%, respectively, P < 0.05). In conclusion, p16(INK4A) and p14(ARF) mRNA expression was frequently increased in haematological malignancies, especially in CML. We suggest that overexpression of these mRNAs may be related to the pathogenesis of haematological malignancies.