Regressing atypical histiocytosis: the controversy continues

Dehner, Louis P.

doi:10.1001/archderm.124.3.319

Cited by 10 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[61][62][63][64][65] However, findings of MFH-specific genomic alterations 66 -68 and gene expression profiles 69 -71 indicate that diagnosis of UPS/MFH corresponds to a distinct nosological entity and may reflect development of these neoplasms from MSC.…”

Section: Discussionmentioning

confidence: 99%

Local Mesenchymal Stem/Progenitor Cells Are a Preferential Target for Initiation of Adult Soft Tissue Sarcomas Associated with p53 and Rb Deficiency

Choi

Curtis

Roy

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

The cell of origin and pathogenesis of the majority of adult soft tissue sarcomas (STS) remains poorly understood. Because mutations in both the P53 and RB tumor suppressor genes are frequent in STS in humans, we inactivated these genes by Cre-loxP-mediated recombination in mice with floxed p53 and Rb. Ninety-three percent of mice developed spindle cell/ pleomorphic sarcomas after a single subcutaneous injection of adenovirus carrying Cre-recombinase. Similar to human STS, these sarcomas overexpress Cxcr4, which contributes to their invasive properties. Using irradiation chimeras generated by transplanting bone marrow cells from mice carrying either the Rosa26Stop loxP LacZ or the Z/EG reporter , as well as the floxed p53 and Rb genes , into irradiated p53 loxP/loxP Rb loxP/loxP mice, it was determined that sarcomas do not originate from bone marrow-derived cells, such as macrophages, but arise from the local resident cells. At the same time , dermal mesenchymal stem cells isolated by strict plastic adherence and low levels of Sca-1 expression (Sca-1 low , CD31 neg CD45 neg ) have shown enhanced potential for malignant transformation according to soft agar, invasion, and tumorigenicity assays, after the conditional inactivation of both p53 and Rb. Sarcomas formed after transplantation of these cells have features typical for undifferentiated high-grade pleomorphic sarcomas. Taken together, our studies indicate that local Sca-1 low dermal mesenchymal stem/progenitor cells are preferential targets for malignant transformation associated with deficiencies in both p53 and Rb. (Am J

show abstract

Section: Discussionmentioning

confidence: 99%