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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1720-1727.
Prepublished online as a Blood First Edition Paper on October 26, 2006; DOI 10.1182/blood-2006-04-018143.
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NEOPLASIA
Gene-expression profiling and array-based CGH classify CD4+CD56+ hematodermic neoplasm and cutaneous myelomonocytic leukemia as distinct disease entities
Remco Dijkman1,
Remco van Doorn1,
Károly Szuhai2,
Rein Willemze1,
Maarten H. Vermeer1, and
Cornelis P. Tensen1
1 Department of Dermatology and
2 Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands
CD4+CD56+ hematodermic neoplasm (CD4+CD56+HN) is an aggressive hematopoietic malignancy with distinct clinicopathologic and immunophenotypic features that commonly involve the skin, bone marrow, and blood. Differentiation from cutaneous myelomonocytic leukemia (c-AML) may be exceedingly difficult and requires extensive phenotyping. The molecular mechanisms involved in the development of CD4+CD56+HN are largely unresolved. Moreover, recurrent chromosomal alterations have not yet been precisely defined in CD4+CD56+HN and c-AML. In the present study an integrated genomic analysis using expression profiling and array-based comparative genomic hybridization (CGH) was performed on lesional skin biopsy samples of patients with CD4+CD56+HN and c-AML. Our results demonstrate that CD4+CD56+HN and c-AML show distinct gene-expression profiles and distinct patterns of chromosomal aberrations. CD4+CD56+HN is characterized by recurrent deletion of regions on chromosome 4 (4q34), chromosome 9 (9p13-p11 and 9q12-q34), and chromosome 13 (13q12-q31) that contain several tumor suppressor genes with diminished expression (Rb1, LATS2). Elevated expression of the oncogenes HES6, RUNX2, and FLT3 was found but was not associated with genomic amplification. We noted high expression of various plasmacytoid dendritic-cell (pDC)–related genes, pointing to the cell of origin of this malignancy.
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