Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1

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...

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Bibliographic Details
Published in:Blood 1998-07, Vol.92 (1), p.267-272
Main Authors: SIDE, L. E, EMANUEL, P. D, TAYLOR, B, FRANKLIN, J, THOMPSON, P, CASTLEBERRY, R. P, SHANNON, K. M
Format: Article
Language:English
Subjects:
Biological and medical sciences
Child, Preschool
Female
Hematologic and hematopoietic diseases
Humans
Infant
Leukemia, Myelomonocytic, Chronic - genetics
Leukemia, Myelomonocytic, Chronic - physiopathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Mutation
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - physiopathology
Neurofibromatosis 1 - genetics
Neurofibromatosis 1 - physiopathology
Neurofibromin 1
Proteins - genetics
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V92.1.267.413a31_267_272