Evidence for reduced B-cell progenitors in early (low-risk) myelodysplastic syndrome.
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.
Sternberg
Alexander
A
Department of Hematology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom OX3 9DU.
Killick
Sally
S
Littlewood
Tim
T
Hatton
Chris
C
Peniket
Andy
A
Seidl
Thomas
T
Soneji
Shamit
S
Leach
Joanne
J
Bowen
David
D
Chapman
Claire
C
Standen
Graham
G
Massey
Edwin
E
Robinson
Lisa
L
Vadher
Bipin
B
Kaczmarski
Richard
R
Janmohammed
Riaz
R
Clipsham
Kim
K
Carr
Andrew
A
Vyas
Paresh
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013234:Stem Cells / Q000473:pathology; D013997:Time Factors
D018952:Antigens, CD34; D018076:DNA, Complementary; D012333:RNA, Messenger