Gene-expression profiling and array-based CGH classify CD4+CD56+ hematodermic neoplasm and cutaneous myelomonocytic leukemia as distinct disease entities
- 26 October 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 109 (4), 1720-1727
- https://doi.org/10.1182/blood-2006-04-018143
Abstract
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.Keywords
This publication has 29 references indexed in Scilit:
- Two categories of mammalian galactose-binding receptors distinguished by glycan array profilingGlycobiology, 2006
- Array-Based Comparative Genomic Hybridization Analysis Reveals Recurrent Chromosomal Alterations and Prognostic Parameters in Primary Cutaneous Large B-Cell LymphomaJournal of Clinical Oncology, 2006
- WHO-EORTC classification for cutaneous lymphomasBlood, 2005
- The ETS Transcription Factor Spi-B Is Required for Human Plasmacytoid Dendritic Cell DevelopmentThe Journal of Experimental Medicine, 2004
- Insights from genomic microarrays into structural chromosome rearrangementsAmerican Journal of Medical Genetics Part A, 2004
- Genomic Alterations in Blastic Natural Killer/Extranodal Natural Killer-Like T Cell Lymphoma with Cutaneous InvolvementJournal of Investigative Dermatology, 2003
- The role of FLT3 in haematopoietic malignanciesNature Reviews Cancer, 2003
- CD4+, CD56+ DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe Francais de Cytogenetique HematologiqueBlood, 2002
- Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial AntigensThe Journal of Experimental Medicine, 2001
- Identification of a leukemic counterpart of the plasmacytoid dendritic cellsBlood, 2001