Enhanced HDAC (Histone Deacetylase) Enzyme Activities in Blood CD 34 ⁺ Cells in Patients with Agnogenic Myeloid Metaplasia.

We previously reported that Blood TIMP-1, TPO levels are elevated and blood MMP-3, bone marrow SDF-1 levels are decreased in patients with Agnogenic Myeloid Metaplasia (AMM). We postulated that these finding are likely related to the defects in TGF-β 1 pathway especially the TGF-β Type II (TGF β RII) receptor defects, resulting in enhanced TGF-β 1 activity. Decreased TGF β RII mRNA has been reported in blood CD 34 ⁺ cells previously. HDAC have been found lately to play an important role in the transcriptional repression and silencing of genes in cancer and HDAC inhibitors have proven to be useful tools in the treatment of cancer by reversre the silenced genes. We therefore measured HDAC activity in Blood CD 34 ⁺ cells to further explore the mechanism of the TGF β R II defects in this disease. HDAC activity was measured using the HDAC Colorimetric Activity Assay/Drug discovery Kit (BIOMOL Research Lab. Inc. PA). Nine patients with AMM and other patients with myeloproliferative diseases and normal volunteers used as controls were studied. The HDAC activities were expressed as the amount of the released Deacetylated Products (uM) as shown in Table 1.

This preliminary study suggests that HDAC activity is enhanced in some patients with AMM, and could be responsible for the decreased TGF β RII expression. HDAC inhibitors could therefore serve as valuable tools in the treatment of this disease.

Table 1