Experimental Hematology
Volume 38, Issue 9 , Pages 718-732.e6 , September 2010

Identification of defects in the transcriptional program during lineage-specific in vitro differentiation of CD34+ cells selected from patients with both low- and high-risk myelodysplastic syndrome

  • Saskia Gueller

      Affiliations

    • Department of Hematology and Oncology, University Hospital, Frankfurt/Main, Germany
    • Drs. Gueller and Komor contributed equally to this work.
  • ,
  • Martina Komor

      Affiliations

    • Department of Hematology and Oncology, University Hospital, Frankfurt/Main, Germany
    • Drs. Gueller and Komor contributed equally to this work.
  • ,
  • Daniel Nowak

      Affiliations

    • Department of Hematology and Oncology, University Hospital, Mannheim, Germany
  • ,
  • Claudia D. Baldus

      Affiliations

    • Department of Hematology and Oncology, University Hospital, Mannheim, Germany
  • ,
  • Sven de Vos

      Affiliations

    • Division of Hematology/Oncology, UCLA School of Medicine, Los Angeles, Calif., USA
  • ,
  • Dieter Hoelzer

      Affiliations

    • Department of Hematology and Oncology, University Hospital, Frankfurt/Main, Germany
  • ,
  • Oliver G. Ottmann

      Affiliations

    • Department of Hematology and Oncology, University Hospital, Frankfurt/Main, Germany
  • ,
  • Wolf-K. Hofmann

      Affiliations

    • Department of Hematology and Oncology, University Hospital, Mannheim, Germany
    • Corresponding Author InformationOffprint requests to: Wolf-K. Hofmann, M.D., Ph.D., Department of Hematology and Oncology, University Hospital, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany

Received 1 September 2009 ,Revised 1 April 2010 ,Accepted 27 April 2010.

References 

  1. Hofmann WK, Koeffler HP. Important features of myelodysplastic syndrome. Int J Hematol. 2002;76(Suppl 2):222–227
  2. Hofmann WK, Koeffler HP. Myelodysplastic syndrome. Annu Rev Med. 2005;56:1–16
  3. Parker J, Mufti GJ. Ras and myelodysplasia: lessons from the last decade. Semin Hematol. 1996;33:206–224
  4. Saitoh K, Miura I, Takahashi N, Miura AB. Fluorescence in situ hybridization of progenitor cells obtained by fluorescence-activated cell sorting for the detection of cells affected by chromosome abnormality trisomy 8 in patients with myelodysplastic syndromes. Blood. 1998;92:2886–2892
  5. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–2088
  6. Komor M, Guller S, Baldus CD, et al. Transcriptional profiling of human hematopoiesis during in vitro lineage-specific differentiation. Stem Cells. 2005;23:1154–1169
  7. Hofmann WK, de VS, Komor M, Hoelzer D, Wachsman W, Koeffler HP. Characterization of gene expression of CD34+ cells from normal and myelodysplastic bone marrow. Blood. 2002;100:3553–3560
  8. Al-Shahrour F, Diaz-Uriarte R, Dopazo J. FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes. Bioinformatics. 2004;20:578–580
  9. Baldus CD, Thiede C, Soucek S, Bloomfield CD, Thiel E, Ehninger G. BAALC expression and FLT3 internal tandem duplication mutations in acute myeloid leukemia patients with normal cytogenetics: prognostic implications. J Clin Oncol. 2006;24:790–797
  10. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–408
  11. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45
  12. Brazma A, Hingamp P, Quackenbush J, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet. 2001;29:365–371
  13. Lee YT, Miller LD, Gubin AN, et al. Transcription patterning of uncoupled proliferation and differentiation in myelodysplastic bone marrow with erythroid-focused arrays. Blood. 2001;98:1914–1921
  14. Gersuk GM, Lee JW, Beckham CA, Anderson J, Deeg HJ. Fas (CD95) receptor and Fas-ligand expression in bone marrow cells from patients with myelodysplastic syndrome. Blood. 1996;88:1122–1123
  15. Raza A, Gregory SA, Preisler HD. The myelodysplastic syndromes in 1996: complex stem cell disorders confounded by dual actions of cytokines. Leuk Res. 1996;20:881–890
  16. Fontenay-Roupie M, Bouscary D, Guesnu M, et al. Ineffective erythropoiesis in myelodysplastic syndromes: correlation with Fas expression but not with lack of erythropoietin receptor signal transduction. Br J Haematol. 1999;106:464–473
  17. Bouscary D, De VJ, Guesnu M, et al. Fas/Apo-1 (CD95) expression and apoptosis in patients with myelodysplastic syndromes. Leukemia. 1997;11:839–845
  18. Parker JE, Pagliuca A, Mijovic A, et al. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997;99:939–944
  19. Sasaki M, Kotcherguina L, Dharia A, Fujimoto S, Dahiya R. Cytosine-phosphoguanine methylation of estrogen receptors in endometrial cancer. Cancer Res. 2001;61:3262–3266
  20. Heaney ML, Golde DW. Myelodysplasia. N Engl J Med. 1999;340:1649–1660
  21. Mazzone A, Porta C, Fossati G, Gritti D, Mazzucchelli I, Ricevuti G. Granulocyte dysplasia and dysfunction, and CD11/CD18 defects in myelodysplastic syndromes. Leuk Lymphoma. 1996;23:267–275
  22. Pellagatti A, Esoof N, Watkins F, et al. Gene expression profiling in the myelodysplastic syndromes using cDNA microarray technology. Br J Haematol. 2004;125:576–583
  23. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 1998;93:705–716
  24. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994;107:1183–1188
  25. Marnett LJ, DuBois RN. COX-2: a target for colon cancer prevention. Annu Rev Pharmacol Toxicol. 2002;42:55–80
  26. Abdallah BM, Jensen CH, Gutierrez G, Leslie RG, Jensen TG, Kassem M. Regulation of human skeletal stem cells differentiation by Dlk1/Pref-1. J Bone Miner Res. 2004;19:841–852
  27. Laborda J, Sausville EA, Hoffman T, Notario V. dlk, a putative mammalian homeotic gene differentially expressed in small cell lung carcinoma and neuroendocrine tumor cell line. J Biol Chem. 1993;268:3817–3820
  28. Smas CM, Sul HS. Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation. Cell. 1993;73:725–734
  29. Van Limpt VA, Chan AJ, Van Sluis PG, Caron HN, Van Noesel CJ, Versteeg R. High delta-like 1 expression in a subset of neuroblastoma cell lines corresponds to a differentiated chromaffin cell type. Int J Cancer. 2003;105:61–69
  30. Schmidt JV, Matteson PG, Jones BK, Guan XJ, Tilghman SM. The Dlk1 and Gtl2 genes are linked and reciprocally imprinted. Genes Dev. 2000;14:1997–2002
  31. Wylie AA, Murphy SK, Orton TC, Jirtle RL. Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulation. Genome Res. 2000;10:1711–1718
  32. Takada S, Paulsen M, Tevendale M, et al. Epigenetic analysis of the Dlk1-Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2-H19. Hum Mol Genet. 2002;11:77–86
  33. Hassan AB, Howell JA. Insulin-like growth factor II supply modifies growth of intestinal adenoma in Apc(Min/+) mice. Cancer Res. 2000;60:1070–1076
  34. Bell AC, Felsenfeld G. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature. 2000;405:482–485
  35. Frevel MA, Sowerby SJ, Petersen GB, Reeve AE. Methylation sequencing analysis refines the region of H19 epimutation in Wilms tumor. J Biol Chem. 1999;274:29331–29340
  36. Nakagawa H, Chadwick RB, Peltomaki P, Plass C, Nakamura Y, de La CA. Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites in colorectal cancer. Proc Natl Acad Sci U S A. 2001;98:591–596
  37. Sullivan MJ, Taniguchi T, Jhee A, Kerr N, Reeve AE. Relaxation of IGF2 imprinting in Wilms tumours associated with specific changes in IGF2 methylation. Oncogene. 1999;18:7527–7534
  38. Langer F, Stickel J, Tessema M, Kreipe H, Lehmann U. Overexpression of delta-like (Dlk) in a subset of myelodysplastic syndrome bone marrow trephines. Leuk Res. 2004;28:1081–1083
  39. Miyazato A, Ueno S, Ohmine K, et al. Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction. Blood. 2001;98:422–427
  40. Li D, Yea S, Li S, et al. Kruppel-like factor-6 promotes preadipocyte differentiation through histone deacetylase 3-dependent repression of DLK1. J Biol Chem. 2005;280:26941–26952
  41. Li L, Forman SJ, Bhatia R. Expression of DLK1 in hematopoietic cells results in inhibition of differentiation and proliferation. Oncogene. 2005;24:4472–4476

PII: S0301-472X(10)00205-5

doi: 10.1016/j.exphem.2010.04.018

Experimental Hematology
Volume 38, Issue 9 , Pages 718-732.e6 , September 2010