p15 protein expression in MDS bone marrow cells is up-regulated with p15 demethylation during decitabine treatment.

(A) Bone marrow biopsy from patient 006 before (left) and after (right) 1 course of treatment; magnification, × 40. Upper panel:p15 staining; lower panel: granulocytes and precursors detected by naphthol AS-D-chloroacetate esterase (NACE) staining. Arrows indicate p15 staining in isolated cells prior to treatment. (B) Patient 001 before (left) and after (right) 3 courses of treatment. Immunohistochemical staining of myeloid precursors was scored semiquantitatively by visual inspection for 3 categories: −, completely negative or only few dispersed positive cells; +, a moderate number of cells stained positive; ++, the majority or all cells stained positive. (C) 8 patients with p15 hypermethylation (> 15%) were examined for p15 expression prior to treatment (white columns) and at time of maximal hypomethylation (gray columns) and 2 patients with p15 methylation lower than 15%. An abnormal karyotype was present prior to treatment in all patients except 006, 017, and 020. Complete reversion to normal karyotype at time of maximal hypomethylation (gray columns, course number given below) occurred only in patient 003.