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Chronic Myeloproliferative Neoplasias

The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence

Leukemia volume 23, pages 892–899 (2009)Cite this article

Abstract

We found that composition of cell subsets within the CD34+ cell population is markedly altered in chronic phase (CP) chronic myeloid leukemia (CML). Specifically, proportions and absolute cell counts of common myeloid progenitors (CMP) and megakaryocyte–erythrocyte progenitors (MEP) are significantly greater in comparison to normal bone marrow whereas absolute numbers of hematopoietic stem cells (HSC) are equal. To understand the basis for this, we performed gene expression profiling (Affymetrix HU-133A 2.0) of the distinct CD34+ cell subsets from six patients with CP CML and five healthy donors. Euclidean distance analysis revealed a remarkable transcriptional similarity between the CML patients’ HSC and normal progenitors, especially CMP. CP CML HSC were transcriptionally more similar to their progeny than normal HSC to theirs, suggesting a more mature phenotype. Hence, the greatest differences between CP CML patients and normal donors were apparent in HSC including downregulation of genes encoding adhesion molecules, transcription factors, regulators of stem-cell fate and inhibitors of cell proliferation in CP CML. Impaired adhesive and migratory capacities were functionally corroborated by fibronectin detachment analysis and transwell assays, respectively. Based on our findings we propose a loss of quiescence of the CML HSC on detachment from the niche leading to expansion of myeloid progenitors.

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Acknowledgements

The following sources of financial support to IB and AC are greatly appreciated: Leukämie Liga e.V. Düsseldorf, Forschungskommission der Medizinischen Fakultät Düsseldorf. We thank Anne Koch and Sabrina Pechtel for excellent technical assistance and Dr Bernd Giebel and Dr Frank Neumann for fruitful discussions.

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Authors and Affiliations

  1. Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University Düsseldorf, Duesseldorf, Germany

    I Bruns, A Czibere, R-P Cadeddu, S Buest, D Bruennert, R Singh, G Kobbe, N Gattermann, R Kronenwett & R Haas

  2. Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Düsseldorf, Duesseldorf, Germany

    J C Fischer

  3. Theoretical Bioinformatics, German Cancer Research Center, Heidelberg, Germany

    F Roels & B Brors

  4. Städtische Kliniken Neuss, Lukaskrankenhaus, Neuss, Germany

    A N Huenerlituerkoglu

  5. Department of General and Visceral Surgery, Heinrich-Heine-University Düsseldorf, Duesseldorf, Germany

    N H Stoecklein

  6. BIDMC Genomics Center, Harvard Institutes of Medicine, Boston, MA, USA

    L F Zerbini

  7. Department of Orthopedic Surgery, Heinrich-Heine-University Düsseldorf, Duesseldorf, Germany

    M Jäger

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Correspondence to I Bruns.

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Bruns, I., Czibere, A., Fischer, J. et al. The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence. Leukemia 23, 892–899 (2009). https://doi.org/10.1038/leu.2008.392

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