Concomitant Overexpression of P16INK4A and P14ARF in Chronic Myeloid Leukaemia
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- Category: Vol. 77, June 2009
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Concomitant Overexpression of P16INK4A and P14ARF in Chronic Myeloid Leukaemia,KHALID A. NASIF, EBTESAM M. EL-GEZAWY, OSAMA B. SEDEEK and SAMY M. ALY
Abstract
The molecular abnormalities involved in the progression of chronic myeloid leukemia (CML) are poorly understood. Genetic alterations of the INK4A/ARF locus have been im-plicated. Two proteins, P16INK4A and P14ARF, originating from the same gene locus CDKN2A, use different promoters and alternative reading frames. P16INK4A is translated from a transcript and P14ARF is from ß transcript. These two proteins, which are inactivated in some human malignancies, are possible tumour suppressor candidates. P16INK4A inhibits the activities of cyclin-dependent kinases (cdks), which maintain the retinoblastoma protein (pRb) in its active hypo-phosphorylated state resulting in a G1-phase progression towards the S phase. P14ARF binds directly to MDM2 and stabilizes both p53 and MDM2 which induces cell cycle arrest in both G1 and G2/M.
Objective: To investigate the over-expression of P16INK4A and P14ARF 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 IIb) showed barely detectable expression of either mRNA. In contrast, overex-pression of P16INK4A and P14ARF mRNAs was more frequent in CML patients (group I) (81.8% and 72.73%, respectively) than in controls group IIa (p < 0.05 and p < 0.01, respectively) and in controls (group IIb), (p < 0.01 and p < 0.001).
Conclusion: P 16INK4A and P 14ARF mRNA over-expression was frequently increased in CML. The overexpression of these mRNAs may be related to the pathogenesis of CML.