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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1914-1921
NEOPLASIA
Transcription patterning of uncoupled proliferation and
differentiation in myelodysplastic bone marrow with
erythroid-focused arrays
Y. Terry Lee,
Lance D. Miller,
Alexander N. Gubin,
Fairouz Makhlouf,
Urszula Wojda,
A. John Barrett,
Edison T. Liu, and
Jeffery L. Miller
From the Laboratory of Chemical Biology, National
Institute of Diabetes and Digestive and Kidney Diseases; Section of
Molecular Signaling and Oncogenesis, Division of Clinical Sciences,
National Cancer Institute; Center for Information Technology; and
Hematology Branch, National Heart, Lung, and Blood Institute, National
Institutes of Health, Bethesda, MD.
Because abnormal erythroid differentiation is the most common
manifestation of the myelodysplastic syndromes (MDS), it was hypothesized that erythroid gene expression may be used to illustrate myelodysplastic transcription patterns. Ten normal bone marrow aspirates (NBM) were first analyzed using an erythroid-focused cDNA
array to define steady-state transcription levels. Proliferation and
differentiation gene subsets were identified by statistically significant differences between NBM and erythroleukemia gene
expression. Next, cDNAs from 5 separate MDS aspirates were studied:
refractory anemia, refractory anemia with ringed sideroblasts,
refractory anemia with excess blasts, refractory anemia with excess
blasts in transformation (RAEB-T), and RAEB-T/secondary MDS. A
distinct pattern of significantly increased proliferation-associated
and reduced differentiation-associated gene activity was established for MDS.
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