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Published 5 January 2004. doi:10.1084/jem.20031175
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 1, 59-68
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Gene Expression Profiling of Hairy Cell Leukemia Reveals a Phenotype Related to Memory B Cells with Altered Expression of Chemokine and Adhesion Receptors

Katia Basso1, Arcangelo Liso5, Enrico Tiacci5, Roberta Benedetti5, Alessandro Pulsoni6, Robin Foa6, Francesco Di Raimondo7, Achille Ambrosetti8, Andrea Califano4, Ulf Klein1, Riccardo Dalla Favera1,2,3 and Brunangelo Falini5

1 Institute for Cancer Genetics, Columbia University, New York, NY 10032
2 Department of Pathology, Columbia University, New York, NY 10032
3 Department of Genetics and Development, Columbia University, New York, NY 10032
4 Center for Computational Biology and Biochemistry, Columbia University, New York, NY 10032
5 Institute of Hematology, University of Perugia, Perugia 06100, Italy
6 Institute of Hematology, University "La Sapienza," Rome 00100, Italy
7 Institute of Hematology, University of Catania, Catania 95100, Italy
8 Institute of Hematology, Policlinico "Borgo Roma," Verona 37100, Italy

Address correspondence to Brunangelo Falini, Institute of Hematology, Policlinico Monteluce, Perugia 06100, Italy. Phone: 39-075-5731103; Fax: 39-075-5783834; email: faliniem{at}unipg.it

Hairy cell leukemia (HCL) is a chronic B cell malignancy characterized by the diffuse infiltration of bone marrow and spleen by cells displaying a typical "hairy" morphology. However, the nature of the HCL phenotype and its relationship to normal B cells and to other lymphoma subtypes remains unclear. Using gene expression profiling, we show here that HCL displays a homogeneous pattern of gene expression, which is clearly distinct from that of other B cell non-Hodgkin lymphomas. Comparison with the gene expression profiles of purified normal B cell subpopulations, including germinal center (GC), pre-GC (naive), and post-GC (memory) B cells, shows that HCL cells are more related to memory cells, suggesting a derivation from this B cell population. Notably, when compared with memory cells, HCL cells displayed a remarkable conservation in proliferation, apoptosis, and DNA metabolism programs, whereas they appeared significantly altered in the expression of genes controlling cell adhesion and response to chemokines. Finally, these analyses have identified several genes that are specifically expressed in HCL and whose expression was confirmed at the protein level by immunocytochemical analysis of primary HCL cases. These results have biological implications relevant to the pathogenesis of this malignancy as well as clinical implications for its diagnosis and therapy.

Key Words: DNA microarray • germinal center • hairy morphology • marrow fibrosis • homing

A. Liso and E. Tiacci contributed equally to this work.

The online version of this article includes supplemental material.

Abbreviations used in this paper: APAAP, alkaline phosphatase antialkaline phosphatase; B-CLL, B cell chronic lymphocytic leukemia; B-NHL, B cell non-Hodgkin lymphoma; BL, Burkitt lymphoma; DLBCL, diffuse large B cell lymphoma; FL, follicular lymphoma; Gas, growth arrest–specific; GC, germinal center; HCL, hairy cell leukemia; LCL, lymphoblastic cell line; MCL, mantle cell lymphoma; MM, multiple myeloma.


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