Mast cells and the neurofibroma microenvironment

Karl Staser, Feng Chun Yang, D. Clapp

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Neurofibromatosis type 1 (NF1) is the most common genetic disorder with a predisposition to malignancy and affects 1 in 3500 persons worldwide. NF1 is caused by a mutation in the NF1 tumor suppressor gene that encodes the protein neurofibromin. Patients with NF1 have cutaneous, diffuse, and plexiform neurofibromas, tumors comprised primarily of Schwann cells, blood vessels, fibroblasts, and mast cells. Studies from human and murine models that closely recapitulate human plexiform neurofibroma formation indicate that tumorigenesis necessitates NF1 loss of heterozygosity in the Schwann cell. In addition, our most recent studies with bone marrow transplantation and pharmacologic experiments implicate haploinsufficiency of Nf1 (Nf1+/-) and c-kit signaling in the hematopoietic system as required and sufficient for tumor progression. Here, we review recent studies implicating the hematopoietic system in plexiform neurofibroma genesis, delineate the physiology of stem cell factor-dependent hematopoietic cells and their contribution to the neurofibroma microenvironment, and highlight the application of this research toward the first successful, targeted medical treatment of a patient with a nonresectable and debilitating neurofibroma. Finally, we emphasize the importance of the tumor microenvironment hypothesis, asserting that tumorigenic cells in the neurofibroma do not arise and grow in isolation.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalBlood
Volume116
Issue number2
DOIs
StatePublished - Jul 15 2010

Fingerprint

Cellular Microenvironment
Neurofibroma
Neurofibromatosis 1
Mast Cells
Plexiform Neurofibroma
Tumors
Hematopoietic System
Schwann Cells
Neurofibromin 1
Cells
Stem Cell Factor
Physiology
Blood vessels
Fibroblasts
Haploinsufficiency
Neoplasms
Inborn Genetic Diseases
Tumor Microenvironment
Loss of Heterozygosity
Bone

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Mast cells and the neurofibroma microenvironment. / Staser, Karl; Yang, Feng Chun; Clapp, D.

In: Blood, Vol. 116, No. 2, 15.07.2010, p. 157-164.

Research output: Contribution to journalArticle

Staser, Karl ; Yang, Feng Chun ; Clapp, D. / Mast cells and the neurofibroma microenvironment. In: Blood. 2010 ; Vol. 116, No. 2. pp. 157-164.
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