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Myelodysplasia (MDS) is a heterogeneous disorder characterised by bone marrow failure and progression to acute myeloid leukaemia where the molecular and cellular haematopoietic defects are poorly understood. To gain insight into this the pathogenesis of this condition, we analyzed gene expression profiles of bone marrow CD34+ stem/progenitor cells from patients with MDS at a early stage in the disease and compared them with profiles from CD34+ cells from 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 samples with non-MDS anaemia. These findings were then confirmed in the original samples and further samples from a new MDS patient group by Taqman Real Time PCR. 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.

Original publication

DOI

10.1016/j.advenzreg.2006.01.019

Type

Journal article

Journal

Adv Enzyme Regul

Publication Date

2006

Volume

46

Pages

98 - 112

Keywords

B-Lymphocytes, Cell Differentiation, Hematopoietic Stem Cells, Humans, Myelodysplastic Syndromes