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Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulating factor
Open accessAbstract
Juvenile myelomonocytic leukemia (JMML) is a lethal disease of young children characterized by hypersensitivity of hematopoietic progenitors to granulocyte-macrophage colony-stimulating factor (GM-CSF). Mutations in PTPN11, which encodes the protein tyrosine phosphatase Shp-2, are common in JMML. We hypothesized that PTPN11 mutations induce hypersensitivity of hematopoietic progenitors to GM-CSF and confer increased GM-CSF–stimulated phospho–extracellular signal-regulated kinase (Erk) levels. To test this hypothesis, the wild-type (WT) and 3 mutant Ptpn11 cDNAs (E76K, D61V, and D61Y) were transduced into murine bone marrow cells to examine GM-CSF–stimulated granulocyte-macrophage colony-forming unit (CFU-GM) growth, macrophage progenitor proliferation, and activation of the Ras signaling pathway. Expression of the Shp-2 mutants induced progenitor cell hypersensitivity to GM-CSF compared with cells transduced with vector alone or WT Shp-2. Macrophage progenitors expressing the Shp-2 mutants displayed both basal and GM-CSF–stimulated hyperproliferation compared with cells transduced with vector alone or WT Shp-2. Consistently, macrophage progenitors transduced with the Shp-2 mutants demonstrated constitutively elevated phospho-Erk levels and sustained activation of phospho-Erk following GM-CSF stimulation compared with vector alone or WT Shp-2. These data support the hypothesis that PTPN11 mutations induce hematopoietic progenitor hypersensitivity to GM-CSF due to hyperactivation of the Ras signaling axis and provide a basis for the GM-CSF signaling pathway as a target for rational drug design in JMML.
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“Such activated SHP2 mutants also induce cytokine hypersensitivity in myeloid progenitors (15,18).”
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Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome
Tartaglia, M., Mehler, E. L., Goldberg, R. B., Zampino, G., Brunner, H. G., Kremer, H., van der Burgt, I., Crosby, A. H., Ion, A., Jeffery, S., et al. (2001) · Nature Genetics · doi:10.1038/ng772 · Cited by 1,736
STATs: Signal Transducers and Activators of Transcription
Ihle, J. N. (1996) · Cell · doi:10.1016/s0092-8674(00)81277-5 · Cited by 1,381
Tartaglia, M., Niemeyer, C. M., Fragale, A., Song, X., Buechner, J., Jung, A., Hählen, K., Hasle, H., Licht, J. D., & Gelb, B. D. (2003) · Nature Genetics · doi:10.1038/ng1156 · Cited by 1,033
Crystal Structure of the Tyrosine Phosphatase SHP-2
Hof, P., Pluskey, S., Dhe‐Paganon, S., Eck, M. J., & Shoelson, S. E. (1998) · Cell · doi:10.1016/s0092-8674(00)80938-1 · Cited by 997
Tartaglia, M., Kalidas, K., Shaw, A. C., Song, X., Musat, D. L., van der Burgt, I., Brunner, H. G., Bertola, D. R., Crosby, A. H., Ion, A., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/340847 · Cited by 801
SH2-Containing Phosphotyrosine Phosphatase as a Target of Protein-Tyrosine Kinases
Feng, G., Hui, C., & Pawson, T. J. (1993) · Science · doi:10.1126/science.8096088 · Cited by 663
Suppression of SHP-2 and ERK Signalling Promotes Self-Renewal of Mouse Embryonic Stem Cells
Burdon, T., Stracey, C., Chambers, I., Nichols, J., & Smith, A. G. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9265 · Cited by 585
Shannon, K., O'Connell, P., Martin, G. A., Paderanga, D., Olson, K., Dinndorf, P. A., & McCormick, F. P. (1994) · New England Journal of Medicine · doi:10.1056/nejm199403033300903 · Cited by 440
Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis
Loh, M. L. (2003) · Blood · doi:10.1182/blood-2003-09-3287 · Cited by 422
Araki, T., Mohi, G., Ismat, F. A., Bronson, R. T., Williams, I. R., Kutok, J. L., Yang, W., Pao, L. I., Gilliland, D. G., Epstein, J. A., et al. (2004) · Nature Medicine · doi:10.1038/nm1084 · Cited by 419
Research works printed but not linked: 1
- Mongomery DC. Design and Analysis of Experiments. 4th ed. Hoboken, NJ: John Wiley & Sons; 1997.
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Ren, Y., Chen, Z., Chen, L., Woods, N. T., Reuther, G. W., Cheng, J. Q., Wang, H., & Wu, J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705789200 · Cited by 18
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Chan, G., & Neel, B. G. (2016) · Springer eBooks · doi:10.1007/978-1-4939-3649-6_4 · Cited by 13
Wang, R., Ma, Y., Du, S., Li, W., Sun, Y., Zhou, H., & Wang, R. (2018) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2018.10.013 · Cited by 14
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Esposito, M. T. (2019) · HemaSphere · doi:10.1097/hs9.0000000000000195 · Cited by 13
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Chaput, D., & Andelfinger, G. (2024) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2024.02.020 · Cited by 12
Zhu, N., Xiao, H., Wang, L., Fu, S., Zhao, C., & Huang, H. (2015) · Future Oncology · doi:10.2217/fon.14.280 · Cited by 12
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Gaipa, G., Bugarin, C., Cianci, P., Sarno, J., Bonaccorso, P., Biondi, A., & Selicorni, A. (2015) · Blood Cancer Journal · doi:10.1038/bcj.2015.52 · Cited by 4
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Yang, F., Tan, Z., Dai, Y., Wang, X., Huang, Z. J., Chen, K., & Wang, S. (2022) · PubMed Central · Cited by 4
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Verbrugge, A. (2005) · Utrecht University Repository (Utrecht University)
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Nabinger, S. C. (2012) · IUScholarWorks (Indiana University) · doi:10.7912/c2/1948
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Zhu, H. (2011) · eScholarship (California Digital Library)
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Schubbert, S., Bollag, G. E., Lyubynska, N., Nguyen, H. T., Kratz, C. P., Zenker, M., Niemeyer, C. M., Molven, A., & Shannon, K. (2007)
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Goodwin, C. B. (2013) · IUScholarWorks (Indiana University) · doi:10.7912/c2/1950
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Goodwin, C. B., & Chan, R. J. (2016) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-3-319-34211-5_7
Self-citationGeissler, K. H. (2017) · International Journal of Hematology and Therapy · doi:10.15436/2381-1404.17.019
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Rivera, D., Naik, U., Wang, W. J., Cuglievan, B., Yin, C. C., & Chen, L. (2023) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.14191
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Metadata
- Authors
- Chan, R. J., Leedy, M. B., Munugalavadla, V., Voorhorst, C. S., Li, Y., Yu, M., & Kapur, R.
- Affiliations
- Indiana University Indianapolis (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-05-01
- Volume
- 105
- Issue
- 9
- Pages
- 3737-3742
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1895012
- OpenAlex
- W1983831457
- Cited by
- 156
- References
- 40
- Citations by year
- 2026: 2 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 9
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL075816)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- juvenile myelomonocytic leukemia, PTPN11 mutation, SHP2, GM-CSF, GM-CSF hypersensitivity, hematopoietic progenitor cells, macrophage progenitors, Ras signaling, ERK activation, CFU-GM, therapeutic target
- MeSH terms
- Animals, Bone Marrow Cells, Hematopoietic Stem Cells, Humans, Mice, Inbred C57BL, Phosphorylation, Transduction, Genetic, Signal Transduction, Leukemia, Myelomonocytic, Chronic, Granulocyte-Macrophage Colony-Stimulating Factor, Protein Tyrosine Phosphatases, Point Mutation, ras Proteins, Intracellular Signaling Peptides and Proteins, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 11
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