Impact on cell to plasma ratio of miR-92a in patients with acute leukemia: in vivo assessment of cell to plasma ratio of miR-92a.

Background: Plasma microRNA (miRNA) has become a promising biomarker for detecting cancer; however, it remains uncertain whether miRNA expression levels in plasma reflect those in tumor cells. Our aim was to determine the biological relevance of miR-92a, which has been implicated as an oncomiR in both plasma and leukemia cells in patients with acute leukemia and to evaluate whether it could be a novel biomarker for monitoring these patients.

Results: We quantified the expression level of miR-92a in both cells and plasma by reverse transcription polymerase chain reaction in 91 patients with acute leukemia.

Anti-proliferative activity of heat shock protein (Hsp) 90 inhibitors via beta-catenin/TCF7L2 pathway in adult T cell leukemia cells.

The aim of this study is to evaluate the effect of heat shock protein 90 (Hsp90) inhibition, and to identify molecular pathways responsible for anti-proliferative effect on adult T cell leukemia/lymphoma (ATL) cells. For Hsp90 inhibition, we used geldanamycin derivates, 17-AAG (17-allylamino-17-demethoxygeldanamycin) and 17-DMAG (17-(dimethylaminoethylamino) 17-demethoxygeldanamycin) in this study. The inhibitory concentration (IC(50)) of 17-AAG in an ATL cell line, designated as TaY, and two HTLV-1 transformed cell lines (MT-2 and MT-4) was 300-700 nM, and that of 17-DMAG was 150-200nM.

The oral iron chelator deferasirox represses signaling through the mTOR in myeloid leukemia cells by enhancing expression of REDD1.

To evaluate the effect of deferasirox in human myeloid leukemia cells, and to identify the molecular pathways responsible for antiproliferative effects on leukemia cells during chelation therapy, we performed gene expression profiling to focus on the pathway involved in the anticancer effect of deferasirox. The inhibitory concentration (IC50) of deferasirox was 17-50 microM in three human myeloid cell lines (K562, U937, and HL60), while those in fresh leukemia cells obtained from four patients it varied from 88 to 172 microM. Gene expression profiling using Affymerix GeneChips (U133 Plus 2.

A network biology approach evaluating the anticancer effects of bortezomib identifies SPARC as a therapeutic target in adult T-cell leukemia cells.

There is a need to identify the regulatory gene interaction of anticancer drugs on target cancer cells. Whole genome expression profiling offers promise in this regard, but can be complicated by the challenge of identifying the genes affected by hundreds to thousands of genes that induce changes in expression. A proteasome inhibitor, bortezomib, could be a potential therapeutic agent in treating adult T-cell leukemia (ATL) patients, however, the underlying mechanism by which bortezomib induces cell death in ATL cells via gene regulatory network has not been fully elucidated.