Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders

N Engl J Med. 1994 Mar 3;330(9):597-601. doi: 10.1056/NEJM199403033300903.


Background: Children with type 1 neurofibromatosis (NF-1) are at increased risk for malignant myeloid disorders. Analysis of the NF-1 gene (NF1) suggests that the function of its product, neurofibromin, is reduced in affected persons and that NF1 belongs to the tumor-suppressor class of recessive cancer genes. This model is consistent with evidence that neurofibromin accelerates the intrinsic guanosine triphosphate-hydrolyzing activity of the Ras family of regulatory proteins. Loss of constitutional heterozygosity has not been reported in the benign tumors associated with NF-1, however, and has only been detected in a few malignant neural-crest tumors and in some tumor-derived cell lines.

Methods: We studied DNA extracted from the bone marrow of 11 children with NF-1 in whom malignant myeloid disorders developed and from parental leukocytes. We used a series of polymorphic markers within and near NF1 to determine whether leukemogenesis was associated with structural alterations of the gene.

Results: Bone marrow samples from five patients showed loss of heterozygosity. In each case, the NF1 allele was inherited from a parent with NF-1 and the normal allele was deleted.

Conclusions: These data provide evidence of NF1 may function as a tumor-suppressor allele in malignant myeloid diseases in children with NF-1 and that neurofibromin is a regulator of ras in early myelopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles*
  • Base Sequence
  • Bone Marrow / metabolism*
  • Child
  • Child, Preschool
  • DNA Primers
  • DNA, Neoplasm / analysis*
  • Female
  • Gene Deletion*
  • Genes, Neurofibromatosis 1*
  • Heterozygote
  • Humans
  • Infant
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelomonocytic, Chronic / genetics
  • Male
  • Molecular Sequence Data
  • Neurofibromatosis 1 / genetics*


  • DNA Primers
  • DNA, Neoplasm