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Blood, 1 November 2005, Vol. 106, No. 9, pp. 2982-2991.
Prepublished online as a Blood First Edition Paper on August 2, 2005; DOI 10.1182/blood-2005-04-1543.


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Submitted April 15, 2005
Accepted June 27, 2005

Evidence for reduced B-cell progenitors in early (low risk) myelodysplastic syndrome

Alexander Sternberg, Sally Killick, Timothy Littlewood, Chris Hatton, Andrew Peniket, Thomas Seidl, Shammit Soneji, Joanne Leach, David Bowen, Claire Chapman, Edwin Massey, Graham Standen, Lisa Robinson, Bipin Vadher, Richard Kaczmarski, Riaz Janmohammed, Kim Clipsham, Andrew Carr, and Paresh Vyas*

MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom; John Radcliffe Hospital, Oxford, United Kingdom
Royal Bournemouth Hospital, Bournemouth, United Kingdom
John Radcliffe Hospital, Oxford, United Kingdom
Institute of Cancer Research, London, United Kingdom
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom
Ninewells Hospital, Dundee, United Kingdom
Leicester Royal Infirmary, Leicester, United Kingdom
Bristol Royal Infirmary, Bristol, United Kingdom
Hereford County Hospital, Hereford, United Kingdom
Princess Alexandra Hospital, Farnborough, United Kingdom
Hillingdon Hospital, London, United Kingdom
Nuffield Orthopaedic Centre, Oxford, United Kingdom

* Corresponding author; email: paresh.vyas{at}imm.ox.ac.uk.

Early, low risk IPSS (International Prognostic Scoring System) myelodysplasia (MDS) is a heterogeneous disorder where the molecular and cellular haematopoietic defects are poorly understood. To gain insight into this condition, we analyzed gene expression profiles of marrow CD34+ progenitor cells from normal karyotype, low blast count MDS patients, age-matched controls and patients with non-MDS anaemia. Given the heterogeneity of early MDS, a surprisingly consistent finding was decreased expression of B-cell lineage affiliated genes in MDS patients compared to normal controls and 3/5 samples with non-MDS anaemia. Both cases of non-MDS anaemia with reduced B-cell gene expression were on chemotherapy. In 25/27 of the original samples and 9 further MDS samples, Taqman Real Time PCR confirmed these data. Flow cytometry on unfractionated marrow from independent samples also demonstrated reduced B-cell progenitors in MDS patients compared to normal controls. These novel findings suggest a common perturbation in early MDS haematopoiesis. They also provide the rationale for a larger study to evaluate the diagnostic utility of reduced B-cell progenitor number as a diagnostic biomarker of early low risk MDS which can pose a diagnostic challenge.


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