Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia

An Erratum to this article was published on 01 August 2003


We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML. Furthermore, we found mutations in PTPN11 in a small percentage of individuals with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML). Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Distribution of mutations in PTPN11 in myeloid disease and Noonan syndrome and their functional effects.


  1. Hasle, H. et al. Leukemia 13, 376–385 (1999).

    CAS  Article  Google Scholar 

  2. Emanuel, P.D., Shannon, K.M. & Castleberry, R.P. Mol. Med. Today 2, 468–475 (1996).

    CAS  Article  Google Scholar 

  3. Noonan, J.A. Am. J. Dis. Child. 116, 373–380 (1968).

    CAS  Article  Google Scholar 

  4. Tartaglia, M. et al. Nat. Genet. 29, 465–468 (2001).

    CAS  Article  Google Scholar 

  5. Choong, K. et al. J. Pediatr. Hematol. Oncol. 21, 523–527 (1999).

    CAS  Article  Google Scholar 

  6. Bader-Meunier, B. et al. J. Pediatr. 130, 885–889 (1997).

    CAS  Article  Google Scholar 

  7. Fukuda, M., Horibe, K., Miyajima, Y., Matsumoto, K. & Nagashima, M. J. Pediatr. Hematol. Oncol. 19, 177–179 (1997).

    CAS  Article  Google Scholar 

  8. Bollag, G. et al. Nat. Genet. 12, 144–148 (1996).

    CAS  Article  Google Scholar 

  9. Hof, P., Pluskey, S., Dhe-Paganon, S., Eck, M.J. & Shoelson, S.E. Cell 92, 441–450 (1998).

    CAS  Article  Google Scholar 

  10. Tartaglia, M. et al. Am. J. Hum. Genet. 70, 1555–1563 (2002).

    CAS  Article  Google Scholar 

Download references


We thank the affected individuals and their families who participated in the study, the physicians who referred the subjects, I. Baumann for reference morphology review, J. Harbott for cytogenetic studies, S. Lassmann for DNA extraction from tissue samples, F. Lecaill for assistance in preparing graphical representation of the SHP-2 mutations and A. Fisher and P. Noellke for statistical analysis. This work was supported in part by grants from Mount Sinai Children's Health Research Center and National Institutes of Health to B.D.G., Progetto di ricerca finalizzata 1% FSN 2002 “Valutazione molecolare e funzionale delle malformazioni e disfunzioni cardiache su base genetica” to M.T. and Deusche José Carreras Leukämie-Stiftung e.V. and Bundesministerium fuer Bildung und Forschung Competence Network: Pediatric Oncology (Project E: Preleukemic Bone Marrow Disorders) to C.M.N.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Bruce D Gelb.

Ethics declarations

Competing interests

M.T. and B.D.G. have a patent application pending concerning mutations in PTPN11 and Noonan syndrome. M.T., C.M.N. and B.D.G. have a patent application pending concerning mutations in PTPN11 and myeloid disorders.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Tartaglia, M., Niemeyer, C., Fragale, A. et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 34, 148–150 (2003).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing