Modulation of neurofibromatosis type 1 gene expression during in vitro myoblast differentiation

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 NF1gene 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 NF1mutations that resulted in a truncated protein. Single-stranded conformational polymorphism analysis was used to detect RASpoint mutations in these samples. We confirmed mutations of NF1in three leukemias, one of which also showed loss of the normalNF1 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 RASmutations 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.

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Serum mitogenic activity on in vitro glial cells in Neurofibromatosis type 1

Brain Research ◽

10.1016/s0006-8993(98)00016-x ◽

1998 ◽

Vol 793 (1-2) ◽

pp. 21-28 ◽

Cited By ~ 1

Author(s):

Brunella Caronti ◽

Francesca Romana Buttarelli ◽

Sandra Giustini ◽

Caterina Calderaro ◽

Luigi Calandriello ◽

...

Keyword(s):

Glial Cells ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Mitogenic Activity

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Evaluation of copy number variation and gene expression in neurofibromatosis type-1-associated malignant peripheral nerve sheath tumours

Human Genomics ◽

10.1186/s40246-015-0025-3 ◽

2015 ◽

Vol 9 (1) ◽

pp. 3 ◽

Cited By ~ 13

Author(s):

Laura E Thomas ◽

Jincy Winston ◽

Ellie Rad ◽

Matthew Mort ◽

Kayleigh M Dodd ◽

...

Keyword(s):

Gene Expression ◽

Peripheral Nerve ◽

Copy Number Variation ◽

Neurofibromatosis Type 1 ◽

Copy Number ◽

Neurofibromatosis Type ◽

Nerve Sheath ◽

Number Variation

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Reduced Brain Neurofibromatosis Type 1 (Nf1) Tumor Suppressor Gene Expression Confers Differential Sensitivity to Ionizing Radiation In Vivo

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2013.06.1665 ◽

2013 ◽

Vol 87 (2) ◽

pp. S630

Author(s):

A.J. Apicelli ◽

C.G. Robinson ◽

J.R. Simpson ◽

D.H. Gutmann

Keyword(s):

Gene Expression ◽

Tumor Suppressor ◽

Ionizing Radiation ◽

Tumor Suppressor Gene ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Suppressor Gene ◽

Differential Sensitivity

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Neurofibromin-deficient fibroblasts fail to form perineurium in vitro

Development ◽

10.1242/dev.121.11.3583 ◽

1995 ◽

Vol 121 (11) ◽

pp. 3583-3592

Author(s):

T. Rosenbaum ◽

Y.L. Boissy ◽

K. Kombrinck ◽

C.I. Brannan ◽

N.A. Jenkins ◽

...

Keyword(s):

Schwann Cells ◽

Neurofibromatosis Type 1 ◽

Fibroblast Cell ◽

Neurofibromatosis Type ◽

Type I ◽

Nerve Sheath Tumors ◽

Cell Strains ◽

Perineurial Cells

To identify cell type(s) that might contribute to nerve sheath tumors (neurofibromas) in patients with neurofibromatosis type 1, we generated cell cultures containing neurons. Schwann cells and fibroblasts from transgenic mouse embryos in which the type 1 neurofibromatosis gene was disrupted by homologous recombination (Brannan et al. (1994) Genes Development, 8,1019-1029). Normal fascicle formation by perineurial cells failed to occur in the absence of neurofibromin. Fascicles were reduced in number and showed abnormal morphology when normal neurons and Schwann cells were cultured up to 37 days with fibroblasts lacking neurofibromin. Proliferation was increased in a majority of fibroblast cell strains analyzed from embryos lacking neurofibromin. These observations suggest that mutations in the neurofibromatosis type I gene affect fibroblast behavior that might contribute to neurofibroma formation in patients with neurofibromatosis type 1.

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TATA-Binding Protein (TBP)-Like Factor (TLF) Is a Functional Regulator of Transcription: Reciprocal Regulation of the Neurofibromatosis Type 1 and c-fos Genes by TLF/TRF2 and TBP

Molecular and Cellular Biology ◽

10.1128/mcb.25.7.2632-2643.2005 ◽

2005 ◽

Vol 25 (7) ◽

pp. 2632-2643 ◽

Cited By ~ 32

Author(s):

Jayhong A. Chong ◽

Magdalene M. Moran ◽

Martin Teichmann ◽

J. Stefan Kaczmarek ◽

Robert Roeder ◽

...

Keyword(s):

Neurofibromatosis Type 1 ◽

Binding Protein ◽

Neurofibromatosis Type ◽

Tata Binding Protein ◽

Related Factor ◽

Reciprocal Regulation ◽

In Cells

ABSTRACT The lack of direct targets for TATA-binding protein (TBP)-like factors (TLFs) confounds the understanding of their role in gene expression. Here we report that human TLF (also called TBP-related factor 2 [TRF2]) activates a number of different genes, including the neurofibromatosis type 1 (NF1) gene. The overexpression of TLF increases the amount of NF1 mRNA in cells. In vivo, TLF binds to and upregulates transcription from a fragment of the NF1 promoter. In vitro, purified TLF-TFIIA binds directly to the same NF1 promoter fragment that is required for TLF responsiveness in cells. Furthermore, targeted deletion of TLF in mice reduces NF1 levels. In contrast, TLF inhibits transcription driven by a fragment from the TATA-containing c-fos promoter by sequestering TFIIA. TBP affects the NF1 and c-fos promoters in a manner reciprocal to that of TLF, stimulating the c-fos promoter and inhibiting NF1 transcription. We conclude that TLF is a functional regulator of transcription with targets distinct from those of TBP.

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