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IntroductionMyelodysplastic syndrome (MDS) is a slowly progressing leukemic disorder that predominantly affects elderly people. 1,2 Individuals with MDS exhibit cytopenia in at least one lineage of peripheral blood (PB) cells. However, the bone marrow (BM) of many affected individuals is hyper-to normocellular, suggesting the presence of ineffective hematopoiesis. Another characteristic feature of MDS is the dysplasia of at least one lineage (myeloid, erythroid, or megakaryocyte-platelet lineage) of BM cells, such as neutrophils with pseudo-Pelger anomaly, hypersegmented neutrophils, ringed sideroblasts, and micromegakaryocytes. 3 The clinical course of MDS can be divided into several phases. Patients in the indolent, chronic phase exhibit a decrease in the number of PB cells and are diagnosed with either refractory anemia (RA) or RA with ringed sideroblasts (RARS). Individuals with dysplastic change in BM and monocytosis in PB are diagnosed with chronic myelomonocytic leukemia (CMMoL). After a variable interval, however, some individuals with MDS undergo a progressive transformation to overt leukemia. As the number of blast cells increases, the patients are diagnosed with RA with an excess of blasts (RAEB; 5%-19% blasts in BM), RAEB in transformation (RAEB-t; 20%-29% blasts in BM), and, finally, MDS-associated acute leukemia (Ͼ 20% blasts in BM).MDS-associated leukemia is rarely cured by conventional chemotherapy. Intensive treatment with anticancer drugs often results in prolonged myelosuppression, which is one of the main causes of disease-related death. 4 Individuals with acute leukemia that results from MDS therefore have a poor prognosis, which contrasts with the somewhat better outcome of de novo acute myeloid leukemia (AML) in this older group of patients. It is thus essential to differentiate MDS-associated leukemia from de novo AML to select the optimal therapeutic strategy.This task is complicated, however, by the fact that some patients with de novo AML may exhibit dysplastic changes in BM during the course of their disease. [5][6][7] It is thus extremely difficult to diagnose elderly individuals with overt leukemia if their BM exhibits dysplasia. The occurrence of a period of cytopenia before the development of leukemia indicates that the patient should be treated for MDS-associated leukemia. Without the clinical history, however, there are currently few other criteria with which to differentiate MDS-associated leukemia from de novo AML with The development of DNA microarrays or DNA chips has revolutionized the analysis of gene expression profiles. Such DNA microarrays can contain tens of thousands of test complementary DNAs (cDNAs) or oligonucleotides and, with a single hybridization step, allow a systematic comparison of the expression of the corresponding genes between 2 given samples. 8 The completion of the human genome sequencing project will increase further the analytical power of this technology. The use of DNA microarrays has already allowed the identification of candidate mammalian genes ...

Hematopoietic effects of interferon-␥ (IFN-␥) may be responsible for certain aspects of the pathology seen in bone marrow failure syndromes, including aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and some forms of myelodysplasia (MDS). Overexpression of and hematopoietic inhibition by IFN-␥ has been observed in all of these conditions. In vitro, IFN-␥ exhibits strong inhibitory effects on hematopoietic progenitor and stem cells. Previously, we have studied the transcriptome of CD34 cells derived from patients with bone marrow failure syndromes and identified characteristic molecular signatures common to some of these conditions. In this report, we have investigated genomewide expression patterns after exposure of CD34 and bone marrow stroma cells derived from normal bone marrow to IFN-␥ in vitro and have detected profound changes in the transcription profile. Some of these changes were concordant in both stroma and CD34 cells, whereas others were specific to CD34 cells. In