Fibroblast growth factor-2 (FGF-2) is a growth and survival factor whose expression is elevated in many hematopoietic malignancies. A natural antisense RNA (FGF-AS) has been implicated in the posttranscriptional regulation of FGF-2 mRNA expression. We demonstrate for the first time that FGF sense and antisense RNAs are coordinately expressed and translated in hematopoietic cells and tissues. Cytokine stimulation of growth-arrested K562 cells elicited a rapid transient increase in FGF-AS mRNA expression followed by a slower but sustained increase in FGF-2 mRNA. This was accompanied by a marked increase in the expression and nuclear translocation of FGF-2 and the FGF-AS encoded protein, GFG/NUDT6. These findings suggest a role for both FGF-2 and GFG proteins in the cell survival and proliferation of lymphoid and myeloid tumor cells.