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ABSTRACT Individuals with neurofibromatosis type 1 (NF1) are predisposed to certain cancers including juvenile chronic myelogenous leukaemia (JCML). The _NF1_ tumour-suppressor gene encodes

a protein (neurofibromin) that accelerates GTP hydrolysis on Ras proteins. Here we show that primary leukaemic cells from children with NF1 show a selective decrease in NF1-like GTPase

activating protein (GAP) activity for Ras but retain normal cellular GAP activity. Leukaemic cells also show an elevated percentage of Ras in the GTP-bound conformation. JCML cells are

hypersensitive to granulocyte-macrophage colony stimulating factor (GM-CSF), and we observed a similar pattern of aberrant growth in haematopoietic cells from Nf1−/− mouse embryos. These

data define a specific role for neurofibromin in negatively regulating GM-CSF signaling through Ras in haematopoietic cells and they suggest that hypersensitivity to GM-CSF may be a primary

event in the development of JCML. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your

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our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS NEUROFIBROMIN AND SUPPRESSION OF TUMORIGENESIS: BEYOND THE GAP Article 23 January 2022 ONCOGENIC RAS PROMOTES

LEUKEMIC TRANSFORMATION OF CUX1-DEFICIENT CELLS Article 01 February 2023 ONCOGENIC AND MICROENVIRONMENTAL SIGNALS DRIVE CELL TYPE SPECIFIC APOPTOSIS RESISTANCE IN JUVENILE MYELOMONOCYTIC

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719–723 (1990). Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Onyx Pharmaceuticals, 3031 Research Drive, Richmond, California, 94806, USA

Gideon Bollag * Herman B. Wells Research Center, Riley Children's Hospital, Indiana University Medical Center, 702 Barnhill, Indianapolis, Indiana, 46202, USA D. Wade Clapp & You

Yan Zhang * Howard Hughes Medical Institute and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA Shane Shih, Frank McCormick & 

Tyler Jacks * Department of Pediatrics, University of California, San Francisco, California, 94143-0519, USA Felix Adler, Patricia Thompson & Kevin Shannon * Division of Hematology

Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA Beverly J. Lange * Division of Hematology Oncology, Hospital for Sick Children, Toronto, Ontario,

M5G1X8, Canada Melvin H. Freedman Authors * Gideon Bollag View author publications You can also search for this author inPubMed Google Scholar * D. Wade Clapp View author publications You

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for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Bollag, G., Clapp, D., Shih, S. _et al._ Loss of _NF1_ results

in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. _Nat Genet_ 12, 144–148 (1996). https://doi.org/10.1038/ng0296-144 Download citation *

Received: 14 August 1995 * Accepted: 29 November 1995 * Issue Date: 01 February 1996 * DOI: https://doi.org/10.1038/ng0296-144 SHARE THIS ARTICLE Anyone you share the following link with

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