Methylation of the p15INK4b promoter never seems to occur in solid tumors but is a major gene silencing mechanism in hematological malignancies. p14ARF and p16INK4a promoter methylation often occurs in solid tumors but also in leukemias and lymphomas.
Deletions at chromosome 9p21, which harbours the tumour suppressor genes p14/ARF, p15/INK4b, and p16/INK4a, and 17p13, where p53 is located, are associated with the development and progression of lymphomas.
This confirms the p16-methylated status in Hodgkin's cases described in a single previous study and adds information concerning the p15 gene that was also found to be methylated in this lymphoma subtype.
Acute/lymphomatous ATLL has frequent alterations of p15 (20%) and p16 (28-67%), while chronic/smoldering ATLL has fewer abnormalities of p15 (0-13%) and p16 (5-26%).
P15INK4B methylation was studied in the marrows of nine patients (one studied twice) who had been cured of lymphoma and in whom hemopoiesis was believed to be normal.
These results suggest that p16ink4a and p15ink4b methylation could be good markers of disease and could be helpful in identifying lymphoma patients at risk of relapse.
Therefore, considerable efforts have been made to determine the role of CDK4/6-inhibitors in hematologic malignancies: This article will review alterations of components of the cell-cycle machinery in brief and summarize the role of the CDK4/6-inhibitors p16INK4A, p15INK4B, p18INK4C and p19INK4D in leukemias and lymphomas.
These results indicate that the rate of alterations in the p15 and p16 genes is low for lymphomas, but loss of p16 and/or p15 may be involved in the development of some lymphomas.