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Mutations of the NF1 Gene in Children With Juvenile
Myelomonocytic Leukemia Without Clinical Evidence of Neurofibromatosis,
Type 1
Lucy E. Side,
Peter D. Emanuel,
Brigit Taylor,
Janet Franklin,
Patricia Thompson,
Robert P. Castleberry, and
Kevin M. Shannon
From the Department of Pediatrics, University of California, San
Francisco, CA; the Departments of Pediatrics, and Medicine, Division of
Hematology/Oncology, University of Alabama, Birmingham, AL; and the
University of Southern California and Children's Hospital of Los
Angeles, CA.
Juvenile myelomonocytic leukemia (JMML) is a pediatric
myelodysplastic syndrome that is associated with neurofibromatosis, type 1 (NF1). The NF1 tumor suppressor gene encodes
neurofibromin, which regulates the growth of immature myeloid cells by
accelerating guanosine triphosphate hydrolysis on Ras
proteins. The purpose of this study was to determine if the NF1
gene was involved in the pathogenesis of JMML in children without a
clinical diagnosis of NF1. An in vitro transcription and translation
system was used to screen JMML marrows from 20 children for NF1
mutations that resulted in a truncated protein. Single-stranded
conformational polymorphism analysis was used to detect RAS
point mutations in these samples. We confirmed mutations of NF1
in three leukemias, one of which also showed loss of the normal
NF1 allele. An NF1 mutation was detected in normal
tissue from the only patient tested and this suggests that JMML may be
the presenting feature of NF1 in some children. Activating RAS
mutations were found in four patients; as expected, none of these
samples harbored NF1 mutations. Because 10% to 14% of
children with JMML have a clinical diagnosis of NF1, these data are
consistent with the existence of NF1 mutations in approximately
30% of JMML cases.
Blood, Vol. 92 No. 1 (July 1), 1998:
pp. 267-272
© 1998 by The American Society of Hematology.
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