Figure 3.

Main alterations of the INK4 proteins in leukemia and lymphomas. Schematic representation of the hematopoietic tree and main alterations affecting the INK4 proteins in different hematopoietic malignancies. Deletion of p15^INK4b and p16^INK4a together with their 5’ CpG islands hypermethylation in their promoter regions are the most frequent modes of p15^INK4b and of p16^INK4a inactivation in various subtypes of hematopoietic neoplasms including ALL and CLL. Deletion of p18^INK4c has been rarely observed in ALL, whereas it is frequently deleted in MM. p18^INK4c is subjected to a transcriptional repression imposed by the oncofusion protein PML-RARα in APL blasts and it is similarly downregulated by MLL-AF9 in cell lines derived from AML patients.