Pathogenesis of plexiform neurofibroma: Tumor-stromal/hematopoietic interactions in tumor progression

Karl Staser, Feng Chun Yang, D. Wade Clapp

Research output: Contribution to journalReview articlepeer-review

79 Scopus citations


Neurofibromatosis type 1 (NF1) is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene. A second-hit mutation precedes the predominant NF1 neoplasms, which include myeloid leukemia, optic glioma, and plexiform neurofibroma. Despite this requisite NF1 loss of heterozygosity in the tumor cell of origin, nontumorigenic cells contribute to both generalized and specific disease manifestations. In mouse models of plexiform neurofibroma formation, Nf1 haploinsufficient mast cells promote inflammation, accelerating tumor formation and growth. These recruited mast cells, hematopoietic effector cells long known to permeate neurofibroma tissue, mediate key mitogenic signals that contribute to vascular ingrowth, collagen deposition, and tumor growth. Thus, the plexiform neurofibroma microenvironment involves a tumor/stromal interaction with the hematopoietic system that depends, at the molecular level, on a stem cell factor/c-kit-mediated signaling axis. These observations parallel findings in other NF1 disease manifestations and are clearly relevant to medical management of these neurofibromas.

Original languageEnglish (US)
Pages (from-to)469-495
Number of pages27
JournalAnnual Review of Pathology: Mechanisms of Disease
StatePublished - 2012
Externally publishedYes


  • C-kit
  • Mast cell
  • NF1
  • Neurofibromatosis
  • SCF

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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