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Blood, 1 July 2004, Vol. 104, No. 1, pp. 250-255.
Prepublished online as a Blood First Edition Paper on March 11, 2004; DOI 10.1182/blood-2004-01-0181.
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Submitted January 15, 2004
Accepted February 25, 2004
Comparative expressed sequence hybridization studies of hairy cell leukemia show uniform expression profile and imprint of spleen signature
Vera Vanhentenrijk, Chris De Wolf-Peeters, and Iwona Wlodarska*
Division of Morphology and Molecular Pathology, Katholieke Universiteit Leuven, Leuven, Belgium
Center for Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium
* Corresponding author; email: Iwona.Wlodarska{at}uz.kuleuven.ac.be.
CESH, comparative expressed sequence hybridization to chromosomes, is a recently introduced technique that identifies chromosomal regions corresponding to a differential gene expression. This technique is analogous to comparative genomic hybridization (CGH) that detects genomic imbalances. We applied CESH for the study of hairy cell leukemia (HCL), a disorder with a largely unknown expression profile. Twelve HCL cases with spleen involvement were investigated by CESH and CGH. While the latter analysis identified only a few non-recurrent genomic imbalances, CESH showed a consistent expression profile in all HCL cases. In addition, pairing normal spleen with normal lymph node, a "spleen signature was established by CESH. This signature most likely reflects the expression profile of spleen-specific components, such as the sinusoidal lining cells from the red pulp and the marginal zone B cells from the white pulp. Imprint of the "spleen signature" was found in the HCL expression profile, suggesting that HCL may originate from a particular B cell subset present in these splenic components. Besides, pairing HCL with normal lymph node and spleen we identified a "HCL signature" comprising several chromosome regions with altered expression. The most significantly underexpressed regions include 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25 and 17q22-q24, and 13q31 and Xq13.3-q21 were the most significantly overexpressed. These regions possibly harbor genes related to the biology and the pathogenesis of HCL. Their identification warrants further molecular investigations.
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