ABNORMAL RESPONSE OF C-MYC EXPRESSION IN BONE-MARROW CELLS FROM MYELODYSPLASTIC SYNDROME PATIENTS TO PHORBOL ESTER

The abnormal growth and differentiation of bone marrow cells from pati ents with myelodysplastic syndrome (MDS) might be due to impairment of signal transduction pathways leading to an abnormal response to phorb ol ester, eg 12-0-tetradecanoylphorbol 13-acetate (TPA), receptors. Th e impaired signal transduction pathways led to an abnormal response to TPA, determined as the difference in the expression of c-mys before a nd after treatment with TPA. One hour exposure to TPA did not induce c -myc gene expression in normal bone marrow cells. In contrast, the lev els of c-myc gene expression were increased by more than two-fold in M DS bone marrow samples after treatment with TPA. The excess expression of c-myc in MDS samples after exposure to TPA was inhibited by additi on of protein kinase inhibitors (H-7, sphingosine).