Concomitant Overexpression of P16^INK4A and P14^ARF in Chronic Myeloid Leukaemia

The molecular abnormalities involved in the progression of chronic myeloid leukemia (CML) are poorly understood. Genetic alterations of the INK4A/ A RF locus have been implicated. Two proteins, P 161NK4A and P14ARF, originating from the same gene locus CDKN2A, use different promoters and alternative reading frames. P161NK4A is translated from a transcript and P 14ARF is from β transcript. These two proteins, which are inactivated in some human malignancies, are possible tumour suppressor candidates. PI 6INK4A inhibits the activities of cyclin-dependent kinases (cdks), which maintain the retinoblastoma protein (pRb) in its active hypophosphorylated state resulting in a G 1-phase progression towards the S phase. PJ4ARF binds directly to MDM2 and stabilizes both p53 and MDM2 which induces cell cycle anest in both G 1 and 02/M.Objective: To investigate the over-expression of P161NK4A and PJ4ARF in CML. Patients and Methods: We studied 22 patients with CML (group I). Samples of 14 patients with other haematological malignancies (group II a) and 15 healthy donors (group II b) served as controls (group II). P16INK4A and P14ARF mRNA expression was assayed by reverse transcriptase polymerase chain reaction (RT-PCR). Results: The control group (group lib) showed barely detectable expression of either mRNA. In contrast, overexpression of P161NK4A and PJ4ARF mRNAs was more frequent in CML patients (group I) (81.8% and 72.73%, respectively) than in controls group II a (p 0.05 and p O.Dl, respectively) and in controls (group lib), (p 0.01 and p 0.001 ). Conclusion: Pl61NK4A and P14ARF mRNA over-expression was frequently increased in CML. The overexpression of these mRNAs may be related to the pathogenesis of CML.