Gene-expression profiling and array-based CGH classify CD4+CD56+ hematodermic neoplasm and cutaneous myelomonocytic leukemia as distinct disease entities

Abstract

-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.

Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease

“…However, taken together, these data indicate that CD4 þ CD56 þ HDNs are characterized by an unusual genomic profile that is defined by alteration of different targets controlling the same pathway (G1/S transition). These observations are in agreement with those reported recently by Dijkman et al 8 In comparison with this series, our data confirm that recurrent chromosomal alterations involve mainly chromosomes 9 and 13 and delineate a very similar CDR. However, we could not confirm the frequent deletion of chromosomes 4q34.1-4q34.2 or 9p13.2-9p11.2, two regions that did not show altered expression in relation to copy number loss.…”

“…8 These observations indicate that deletion of a gene involved in the G1/S transition pathway that could occur in a pDC or DC2 cell is likely to represent a crucial and early oncogenic step in this disease. As a strong association between classic CD4 þ CD56 þ HDN and myelomonocytic leukaemias has been reported (reviewed in Herling and Jones 6 ), such patterns of TSG loss were unusual in our series of de novo AML, confirming that tumour cells had undergone distinct oncogenic events, as shown earlier by changes in expression levels.…”

“…As a strong association between classic CD4 þ CD56 þ HDN and myelomonocytic leukaemias has been reported (reviewed in Herling and Jones 6 ), such patterns of TSG loss were unusual in our series of de novo AML, confirming that tumour cells had undergone distinct oncogenic events, as shown earlier by changes in expression levels. 8 The delineation of a consensus genomic region in the subgroup of AML with complex karyotype has shown that TP53 and CDKN1B losses can also be frequent in this neoplasm, but not in combination with RB1 deletion. 14 Such combinations are also infrequent in lymphoid neoplasms, as concomitant loss of CDKN2A, RB1 and TP53 was observed in less than 5% of a large panel of various lymphoid malignancies.…”

“…In spite of a very limited number of cases, some candidate genes and their relationship with gene expression profiles were identified. 8 In this study, it was shown that deletions of several tumour suppressor genes (TSG), including RB1, LATS2, CDC14B, DBC1 and SYK, were effectively related to diminished expression. In contrast, some highly expressed oncogenes, such as HES6, RUNX2 and FLT3, were not associated with an increase in gene copy number.…”

“…In contrast, some highly expressed oncogenes, such as HES6, RUNX2 and FLT3, were not associated with an increase in gene copy number. 8 In support of the aim to delineate novel candidate regions and disease-related genes, we studied nine CD4 þ CD56 þ HDN cases using the genome-wide high-resolution array CGH.…”