Gene expression profiling of the bone marrow mononuclear cells from patients with myelodysplastic syndrome.

The gene expression pattern of bone marrow mononuclear cells (BMNCs) from 10 patients with myelodysplastic syndrome (MDS) was studied by two-color cDNA microarray techniques. To confirm the microarray results, a semiquantitative RT-PCR was performed to analyze gene expression in fifty additional MDS patients. Ninety-five genes were shown to be abnormally expressed in at least five MDS patients compared to normal controls, involving cell growth and differentiation regulation, cell cycle control, signaling and redox; such as thrombospondin 1, phosphatase and tensin homolog, MAD, DNA-damage-inducible transcript 3 (DDIT3), ets variant gene 1 (ETV1), and G1 to S phase transition 1. CD36 was also revealed up-regulated in 4 cases. MDS patients in early and advanced stages could be clustered into two distinct groups by hierarchical clustering, wherein a case with isolated thrombocytopenia and other RA patients were clustered into two subgroups. Consistent expression patterns of 3/5 (60%) genes were confirmed by semiquantitative RT-PCR. Further analysis showed the different transcript levels of RNAHP, DDIT3 in patients with MDS in different stages, AML, and normal controls. Meanwhile, the different significance of RNAHP and ETV1 expression was revealed between RA and untypical anaplastic anemia, iron deficiency anemia, and megaloblastic anemia patients. We propose that the technology of microarray may reveal the intrinsic molecular features and the expression levels of RNAHP, DDIT3, and ETV1 may provide useful markers for the diagnosis of MDS.

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