Genes Important for Disease Progression of MDS-Leukemia Revealed by 40K cDNA Microarray.

[Background and Objectives] One of the causes of death in patients with myelodysplastic syndrome (MDS) is leukemic transformation. After the indolent phase, which can be treated with chemotherapy, leukemic MDS will progress to a phase of aggressive blast proliferation, which cannot be controlled by chemotherapy. In this study, we would like to know the molecular mechanisms of the disease progression.

[Materials and Methods] Bone Marrow samples were collected from both indolent (at initial diagnosis) and aggressive (after chemotherapies) phases from 4 MDS-leukemia patients. We extracted RNA from each sample and then amplified the RNA, reverse transcribed the amplified RNA to cDNA, and fluorescently labeled before hybridization for the microarray.

[Results and Discussion] Compared to the expression level at indolent phase, several genes including MEK kinase 5 (ASK1), Rho-associated protein kinase 1 (ROCK1), LIM domain kinase 2 (LIMK2) and GTP binding protein Rheb, were commonly up-regulated more than 2-fold at aggressive phase of 4 cases. These results were confirmed by real time RT-PCR. Since multidrug resistance protein was up-regulated at the ratio of around 1.5, more than 2-fold up-regulation in all 4 examined cases was considered to be significant. These molecules can be candidate markers to predict transition from indolent to aggressive phase of the disease, and also can be targets for novel therapy.