9. A Pluralistic Approach to the Study of Myelodysplastic Syndromes: Evolving Pathology of the Seed via the Soil

  1. Hussain I. Saba MD, PHD3 and
  2. Ghulam J. Mufti MB, DM, FRCP, FRCPATH4
  1. Naomi Galili1,
  2. Raymond Cruz1,
  3. Jamie Stratton1,
  4. Jessica Clima1,
  5. Ghulam Sajjad Khan1 and
  6. Azra Raza2

Published Online: 24 MAR 2011

DOI: 10.1002/9781444394016.ch9

Advances in Malignant Hematology

Advances in Malignant Hematology

How to Cite

Galili, N., Cruz, R., Stratton, J., Clima, J., Sajjad Khan, G. and Raza, A. (2011) A Pluralistic Approach to the Study of Myelodysplastic Syndromes: Evolving Pathology of the Seed via the Soil, in Advances in Malignant Hematology (eds H. I. Saba and G. J. Mufti), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444394016.ch9

Editor Information

  1. 3

    James A. Haley Veterans' Hospital, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, FL, USA

  2. 4

    Department of Haematological Medicine, Guy's and St Thomas' School of Medicine, King's College Hospital, London, UK

Author Information

  1. 1

    St. Vincent's Comprehensive Cancer Center, New York, New York, USA

  2. 2

    Columbia University Medical Center, New York, New York, USA

Publication History

  1. Published Online: 24 MAR 2011
  2. Published Print: 16 APR 2011

ISBN Information

Print ISBN: 9781405196260

Online ISBN: 9781444394016

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Keywords:

  • MDS;
  • excessive proliferation;
  • excessive apoptosis;
  • cell cycle kinetics;
  • ribogenesis;
  • seed and soil;
  • MDS mouse models;
  • systems biology;
  • pro-inflammatory cytokines;
  • BM microenvironment

Summary

Recent biologic insights support the premise that the myelodysplastic syndromes result from a complex series of interactions between a transformed hematopoietic stem cell and its microenvironment. Excessive apoptosis and defective ribogenesis, two of the unifying characteristics across the various syndromes only focus on the stem cell alone. The recurrent genetic mutations of the abnormal stem cells that have been associated with specific chromosomal changes have been used to produce mouse models of MDS, but none faithfully recapitulates the human phenotype. In one model, targeting a mutation to the marrow stromal cell produced an MDS-like disease of the hematopoietic parenchymal cells. Thus, even though the original lesion may occur in one compartment, its expansion into a full-blown clinical syndrome depends on the co-evolving pathology of the other. A reductionist strategy would be inherently inadequate to address such complexity; rather a systems biology approach would be more suited for a pluralistic solution to the problem.