Purpose of review: Tumorigenic cells can co-opt normal functions of nonmalignant hematopoietic cells, promoting tumor progression. Recent mouse and human studies indicate that mast cells underpin inflammation in the plexiform neurofibroma microenvironment of neurofibromatosis type 1. In this model, Nf1 homozygous-deficient Schwann cells recruit hyperactive mast cells, promoting tumorigenesis. Here, we discuss the importance of Nf1 gene dosage, delineate hematopoietic contributions to the plexiform neurofibroma microenvironment, and highlight applications to human treatment. Recent findings: Previous studies found that plexiform neurofibroma formation in a mouse model requires biallelic loss of Nf1 in Schwann cells and an Nf1 heterozygous cellular background. Now, transplantation and pharmacological experiments have indicated that tumor formation specifically requires Nf1 heterozygosity of c-kit-dependent bone marrow. Summary: Neurofibromatosis type 1 results from autosomal dominant mutations of the NF1 tumor suppressor gene. Although unpredictable second-hit mutations in the remaining NF1 allele precede local manifestations such as tumor formation, human and mouse data indicate that NF1/Nf1 gene haploinsufficiency modulates cellular physiology and disease pathogeneses. In particular, Nf1 haploinsufficient mast cells demonstrate multiple gain-in-functions, and mast cells permeate neurofibroma tissue. Transplantation experiments have shown that these aberrant mast cells critically underpin the tumor microenvironment. Using these findings, clinicians have medically treated a patient with a debilitating plexiform neurofibroma.
- mast cells
- neurofibromatosis type 1
- tumor microenvironment
ASJC Scopus subject areas
Plexiform neurofibroma genesis : Questions of Nf1 gene dose and hyperactive mast cells. / Staser, Karl; Yang, Feng Chun; Clapp, D.In: Current Opinion in Hematology, Vol. 17, No. 4, 2010, p. 287-293.
Research output: Contribution to journal › Article
TY - JOUR
T1 - Plexiform neurofibroma genesis
T2 - Questions of Nf1 gene dose and hyperactive mast cells
AU - Staser, Karl
AU - Yang, Feng Chun
AU - Clapp, D.
PY - 2010
Y1 - 2010
N2 - Lippincott Williams & Wilkins.
AB - Lippincott Williams & Wilkins.
KW - c-kit
KW - mast cells
KW - neurofibroma
KW - neurofibromatosis type 1
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=77954072798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954072798&partnerID=8YFLogxK
U2 - 10.1097/MOH.0b013e328339511b
DO - 10.1097/MOH.0b013e328339511b
M3 - Article
VL - 17
SP - 287
EP - 293
JO - Current Opinion in Hematology
JF - Current Opinion in Hematology
SN - 1065-6251
IS - 4