Abstract
Acute myeloid leukemia (AML) may develop de novo or secondarily to myelodysplastic syndrome (MDS). Although the clinical outcome of MDS-related AML is worse than that of de novo AML, it is not easy to differentiate between these two clinical courses without a record of prior MDS. Large-scale profiling of gene expression by DNA microarray analysis is a promising approach with which to identify molecular markers specific to de novo or MDS-related AML. This approach has now been adopted with AC133-positive hematopoietic stem cell-like fractions purified from 10 individuals, each with either de novo or MDS-related AML of the M2 subtype. Sets of genes whose activity was associated with either disease course were identified. Furthermore, on the basis of the expression profiles of these genes, it was possible to predict correctly the clinical diagnosis for 17 (85%) of the 20 cases in a cross-validation trial. Similarly, different sets of genes were identified whose expression level was associated with clinical outcome after induction chemotherapy. These data suggest that, at least in terms of gene expression profiles, de novo AML and MDS-related AML are distinct clinical entities.
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References
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189–199.
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee Meeting – Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17: 3835–3849.
Sole F, Espinet B, Sanz GF, Cervera J, Calasanz MJ, Luno E et al. Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Espanol de Citogenetica Hematologica. Br J Haematol 2000; 108: 346–356.
Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.
Bain BJ . The bone marrow aspirate of healthy subjects. Br J Haematol 1996; 94: 206–209.
Kuriyama K, Tomonaga M, Matsuo T, Ginnai I, Ichimaru M . Diagnostic significance of detecting pseudo-Pelger–Huet anomalies and micro-megakaryocytes in myelodysplastic syndrome. Br J Haematol 1986; 63: 665–669.
Jaffe ES, Harris NL, Stein H, Vardiman JW (eds). Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2001.
Duggan DJ, Bittner M, Chen Y, Meltzer P, Trent JM . Expression profiling using cDNA microarrays. Nat Genet 1999; 21: 10–14.
Hin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997; 90: 5002–5012.
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French–American–British Cooperative Group. Ann Intern Med 1985; 103: 620–625.
Miyazato A, Ueno S, Ohmine K, Ueda M, Yoshida K, Yamashita Y et al. Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction. Blood 2001; 98: 422–427.
Ohmine K, Ota J, Ueda M, Ueno S-I, Yoshida K, Yamashita Y et al. on of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells. Oncogene 2001; 20: 8249–8257.
Van Gelder RN, von Zastrow ME, Yool A, Dement WC, Barchas JD, Eberwine JH . Amplified RNA synthesized from limited quantities of heterogeneous cDNA. Proc Natl Acad Sci USA 1990; 87: 1663–1667.
Alon U, Barkai N, Notterman DA, Gish K, Ybarra S, Mack D et al. Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. Proc Natl Acad Sci USA 1999; 96: 6745–6750.
Valkov NI, Sullivan DM . Drug resistance to DNA topoisomerase I and II inhibitors in human leukemia, lymphoma, and multiple myeloma. Semin Hematol 1997; 34: 48–62.
Moore KA, Pytowski B, Witte L, Hicklin D, Lemischka IR . Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs. Proc Natl Acad Sci USA 1997; 94: 4011–4016.
Chou D, Miyashita T, Mohrenweiser HW, Ueki K, Kastury K, Druck T et al. The BAX gene maps to the glioma candidate region at 19q13.3, but is not altered in human gliomas. Cancer Genet Cytogenet 1996; 88: 136–140.
Piechaczyk M, Blanchard JM, Marty L, Dani C, Panabieres F, Sabouty SE et al. Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues. Nucleic Acid Res 1984; 12: 6951–6963.
Ferbus D, Le Chalony C, Prosperi M-T, Muleris M, Vincent-Salomon A, Goubin G . Identification, nuclear localization, and binding activities of OZF, a human protein solely composed of zinc finger motifs. Eur J Biochem 1996; 236: 991–995.
Yen H-CS, Gordon C, Chang EC . Schizosaccharomyces pombe Int6 and Ras homologs regulate cell division and mitotic fidelity via the proteosome. Cell 2003; 112: 207–217.
Black AR, Black JD, Azizkhan-Clifford J . Sp1 and Kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 2001; 188: 143–160.
Nikiforov YE, Koshoffer A, Nikiforova M, Stringer J, Fagin JA . Chromosomal breakpoint positions suggest a direct role for radiation in inducing illegitimate recombination between the ELE1 and RET genes in radiation-induced thyroid carcinomas. Oncogene 1999; 18: 6330–6334.
Fouraux MA, Kolkman MJ, Van der Heijden A, De Jong AS, Van Venrooij WJ, Pruijn GJ . The human La (SS-B) autoantigen interacts with DDX15/hPrp43, a putative DEAH-box RNA helicase. RNA 2002; 8: 1428–1443.
Hromas R, Cooper S, Broxmeyer HE . The chemokine CCL21 protects normal marrow progenitors from Ara-C cytotoxicity. Cancer Chemother Pharmacol 2002; 50: 163–166.
Hsu HC, Lee YM, Tsai WH, Jiang ML, Ho CH, Ho CK et al. Circulating levels of thrombopoietic and inflammatory cytokines in patients with acute myeloblastic leukemia and myelodysplastic syndrome. Oncology 2002; 63: 64–69.
Little NA, Hastie ND, Davies RC . Identification of WTAP, a novel Wilms' tumour 1-associating protein. Hum Mol Genet 2000; 9: 2231–2239.
Cavailles V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner PJ et al. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J 1995; 14: 3741–3751.
Acknowledgements
We thank all the physicians and patients who participated in the collection of Blast Bank samples. This work was supported in part by grants for Research on the Human Genome, Tissue Engineering, and Food Biotechnology, for the Second-Term Comprehensive 10-Year Strategy for Cancer Control, and for Research on Development of Novel Therapeutic Modalities for Myelodysplastic Syndrome from the Ministry of Health, Labor, and Welfare of Japan; by the Science Research Promotion Fund of the Promotion and Mutual Aid Corporation for Private Schools of Japan; by a grant from Research Foundation for Community Medicine of Japan; by a grant from Sankyo Foundation of Life Science; and by a grant from Takeda Science Foundation. JO is a research resident of the Japan Health Sciences Foundation.
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Oshima, Y., Ueda, M., Yamashita, Y. et al. DNA microarray analysis of hematopoietic stem cell-like fractions from individuals with the M2 subtype of acute myeloid leukemia. Leukemia 17, 1990–1997 (2003). https://doi.org/10.1038/sj.leu.2403098
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DOI: https://doi.org/10.1038/sj.leu.2403098
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