947

CD34

-;CD34 molecule;CD34;CD34 molecule

CD34 antigen|hematopoietic progenitor cell antigen CD34

1q32

protein-coding

Dermatofibrosarcoma protuberans (DP) is a rare, slow growing dermal neoplasm of intermediate malignancy. It is made of spindle-shaped tumor cells in a storiformpattern often positive for CD34. The preferred treatment for DP is a surgical wide excision with pathologically sane margins of 3 cm. At the cytogenetic level, DP cells are characterized by either supernumerary ring chromosomes composed of sequences derived from chromosomes 17 and 22 or more rarely of translocations t(17;22). Rings have been mainly observed in adults whereas translocations have been reported in ALL pediatric cases. These chromosomal rearrangements lead to the formation of a specific fusion gene : COL1A1-PDGFB detected in rings as wellas in translocations. DP is therefore a unique example of tumor in which the same molecular event occurs either on rings or linear translocation derivatives and the chromosomal abnormalities display an age-related pattern. So far, the COL1A1-PDGFB fusion gene remains the only fusion gene identified in this tumor. It is also present in variant forms of DP such as giant cell fibroblastoma, Bednar tumor, adult superficial fibrosarcoma and the granular cell variant of DPdemonstrating that these tumors are not distinct entities but morphological variants of DP. The breakpoint localization in PDGFB was found to be remarkably constant, placing exon 2 of PDGFB under the control of the COL1A1 promoter. In contrast, the COL1A1 breakpoint was found to be variably located within the exons of the alpha-helical coding region (exons 7-47). No correlation between the breakpoint location in COL1A1 and the age of the patient or any clinical or histological particularity has been established. Moreover, no preferential breakpoint appears to be more particularly linked to one or another variant of DP. The COL1A1-PDGFB fusion gene is detectable either by multiplex RT-PCR with acombination of forward primers designed from a variety of COL1A1 exons and one reverse primer for PDGFB exon 2, or by in situ fluorescence hybridization (FISH)on interphase nuclei from frozen or fixed paraffin-embbeded sections. The COL1A1-PDGFB fusion gene is not found in approximately 8% of DP cases, suggesting that genes other than COL1A1 or PDGFB might be involved in a small subset of cases. It has been proposed that PDGFB acts as a mitogen in DP cells by autocrine stimulation of the PDGF receptor. The PDGF receptor tyrosine kinase antagonist imatinib mesylate has recently been used in clinical trials; its efficiency has been demonstrated in several cases, which allows it to be considered as a novel treatment strategy for metastatic or locally advanced DP.

expression of the multidrug resistance (MDR-1) gene product, P-glycoprotein (P-170), and the stem cell antigen, CD34, at diagnosis were determined using monoclonal antibodies (MoAbs) MRK-16 and 12.8 respectively, in 130 pediatric acute myeloid leukemia (AML) patients entered onto childrens cancer Group (CCG) study CCG-2891. Fluorescein isothiocyanate (FITC) as a second step reagent was employed for the measurement of P-170 expression since it is commonly used in clinical laboratories. Nine of 30 (30%) infant ( < 1 year of age) de novo specimens expressed P-170 at levels > or = 20% of control cells. In contrast, eight of 100 (8%) AML samples from older children ( > or = 1 year of age) expressed the multidrug resistance surface protein at diagnosis. With the exception of one infant, ALL de novo samples that expressed P-170 also expressedCD34. pediatric patients of any age with positive P-170 expression using MoAb MRK-16 with a FITC-conjugated second step reagent fared no worse than remaining patients treated on the same treatment with regard to induction failure, incidence of relapse, event-free survival, or overall survival. Further investigation is necessary to determine whether P-170 assay systems with greatersensitivity will distinguish pediatric AML patients with poor prognosis.