p38 Activation correlates with apoptosis in low-grade MDS. Bone marrow biopsies from patients with MDS and non-MDS control subjects were fixed and immunostained with antibody against cleaved or activated caspase-3. Number of apoptotic cells (cleaved caspase-3 positive) were determined in cases of low- and high-risk MDS and compared with controls. (A) Cases of low-risk MDS had significantly higher numbers of apoptotic cells (P < .05, 2 tailed t test). The number of apoptotic cells was correlated with numbers of cells positive for phospho-p38. *Statistical significance. Pearson correlation coefficient was calculated with the use of Microsoft Excel (Redman, WA) (B). Serial sections of a representative MDS bone marrow sample show that cells undergoing apoptosis exhibit greater activation of p38 MAPK (C). Bone marrow biopsies from a representative patient with MDS were stained with rabbit anti–human phospho-p38 (red) and fluorescein-TdT (green) after in situ nucleotide labeling for apoptosis detection (TUNEL assay) followed by goat anti–rabbit IgG Alexa Fluor 568 secondary antibodies. Merged immunofluorescence shows apoptotic cells exhibit activated p38 MAPK (positive for phospho-p38) (D). Arrows indicate positive cells.