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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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CLINICAL TRIALS AND OBSERVATIONS

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

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

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

Early, low-risk International Prognostic Scoring System (IPSS) myelodysplastic syndrome (MDS) is a heterogeneous disorder where the molecular and cellular hematopoietic 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 anemia. Given the heterogeneity of early MDS, a surprisingly consistent finding was decreased expression of B-cell lineage–affiliated genes in MDS patients compared with healthy controls and 3 of 5 samples with non-MDS anemia. Both patients with non-MDS anemia with reduced B-cell gene expression were on chemotherapy. In 25 of 27 of the original samples and 9 further MDS samples, Taqman real-time polymerase chain reaction (PCR) confirmed these data. Flow cytometry on unfractionated marrow from independent samples also demonstrated reduced B-cell progenitors in MDS patients compared with healthy controls. These novel findings suggest a common perturbation in early MDS hematopoiesis. 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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