Skip to main content

Thank you for visiting nature.com. 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.

  • Letter to the Editor
  • Published:

JAK2 V617F mutation is a rare event in juvenile myelomonocytic leukemia

Leukemia volume 21, pages 367–369 (2007)Cite this article

Juvenile myelomonocytic leukemia (JMML) is a unique clonal myelodysplastic/myeloproliferative disorder of infancy and early childhood, characterized by an aggressive clinical course and an extremely poor prognosis for patients who cannot receive an allogeneic hematopoietic stem cell transplantation.1, 2 The disease, usually presenting with leukocytosis and monocytosis, anemia, thrombocytopenia, hepatomegaly and marked splenomegaly, is characterized by an uncontrolled proliferation of monocytic lineage cells. Spontaneous growth of monocyte–macrophage colonies in semisolid media cultures in the absence of added growth factors, as well as a striking hypersensitivity of JMML myeloid progenitors to granulocyte–macrophage colony-stimulating factor (GM-CSF), is a distinctive feature of the disease.1

A pathologic activation of the RAS–RAF–MAP (mitogen-activated protein) kinase signal-transduction pathway from GM-CSF receptor to the nucleus is the key point of the pathophysiology of this disease.3, 4 In about 70% of JMML cases, this activation is due to mutations in RAS (25% of cases), NF1 (clinical diagnosis in about 11% of cases) or PTPN11 (35% of cases).3, 4, 5 All these genetic aberrations have been demonstrated to be able to produce, in experimental models, the development of progressive myeloproliferative disorders.4, 6 However, even though one of these gene mutations can be observed in more than two-thirds of JMML patients, in the remaining affected children a specific genetic alteration has not been identified so far.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Niemeyer CM, Arico’ M, Basso G, Biondi A, Cantu’ Rajnoldi A, Creutzig U et al. Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG-MDS). Blood 1997; 89: 3534–3543.

    CAS  PubMed  Google Scholar 

  2. Locatelli F, Nollke P, Zecca M, Korthof E, Lanino E, Peters C et al. Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial. Blood 2005; 105: 410–419.

    Article  CAS  PubMed  Google Scholar 

  3. Flotho C, Valcamonica S, Mach-Pascual S, Schmahl G, Corral L, Ritterbach J et al. RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia 1999; 13: 32–37.

    Article  CAS  PubMed  Google Scholar 

  4. Le DT, Kong N, Zhu Y, Lauchle JO, Aiyigari A, Braun BS et al. Somatic inactivation of NF1 in hematopoietic cells results in a progressive myeloproliferative disorder. Blood 2004; 103: 4243–4250.

    Article  CAS  PubMed  Google Scholar 

  5. Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 2003; 34: 148–150.

    Article  CAS  PubMed  Google Scholar 

  6. Mohi MG, Williams IR, Dearolf CR, Chan G, Kutok JL, Cohen S et al. Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell 2005; 7: 179–191.

    Article  CAS  PubMed  Google Scholar 

  7. Kralovics R, Passamonti F, Buser AS, Soon-Siog T, Tiedt R, Passweg JR et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352: 1779–1790.

    Article  CAS  PubMed  Google Scholar 

  8. Jelinek J, Oki Y, Gharibyan V, Bueso-Ramos C, Prchal JT, Verstovsek S et al. JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood 2005; 106: 3370–3373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kratz CP, Boll S, Kontny U, Schrappe M, Niemeyer CM, Stanulla M . Mutational screening reveals a novel JAK2 mutation, L611S, in a child with acute lymphoblastic leukemia. Leukemia 2006; 20: 381–383.

    Article  CAS  PubMed  Google Scholar 

  10. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ et al. Activating mutation in the thyrosine kinase JAK2 in polycythemia vera, essential thrombocytemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005; 7: 387–397.

    Article  CAS  PubMed  Google Scholar 

  11. Steensma DP, Dewald GG, Lasho TL, Powell HL, McClure RF, Levine RL et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both ‘atypical’ myeloproliferative disorders and myelodisplastic syndromes. Blood 2005; 106: 1207–1209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Quelle FW, Sato N, Witthuhn BA, Inhorn RC, Eder M, Miyajima A et al. JAK2 associates with the beta chain of the receptors for granulocyte–macrophage colony-stimulating factor, and its activation requires the membrane-proximal region. Mol Cell Biol 1994; 14: 4335–4341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tono C, Xu G, Toki T, Takahaschi Y, Sasaki S, Terui K et al. JAK2 Val617Phe activating thyrosine kinase mutation in juvenile myelomonocytic leukemia. Leukemia 2005; 19: 1843–1844.

    Article  CAS  PubMed  Google Scholar 

  14. Chen CY, Lin LI, Tang JL, Tsay W, Chang HH, Yeh YC et al. Acquisition of JAK2, PTPN11, and RAS mutations during disease progression in primary myelodysplastic syndrome. Leukemia 2006; 20: 1155–1194.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from Ministero della Salute–IRCCS Policlinico San Matteo (Ricerca Corrente grants 80458 and 80125) to MZ and FL and by a private Italian grant in memory of Sofia Luce Rebuffat, to FL

Author information

Authors and Affiliations

  1. Pediatric Hematology/Oncology, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    M Zecca, D Lisini & F Locatelli

  2. Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    G Bergamaschi

  3. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University of Freiburg, Freiburg, Germany

    C Kratz & C M Niemeyer

  4. Department of Oncology, University Children's Hospital, Zürich, Switzerland

    E Bergsträßer

  5. Medical Genetics, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    C Danesino & P De Filippi

  6. Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark

    H Hasle

  7. Pediatric Hematology/Oncology, University of Bologna, Policlinico Sant'Orsola, Bologna, Italy

    A Pession

  8. Pediatric Hematology/Oncology, University of Padova, Padova, Italy

    L Sainati

  9. Pediatric Hematology/Oncology, University Hospital Motol, Prague, Czech Republic

    J Starý

  10. Department of Pediatrics, St Anna Kinderspital, Wien, Austria

    M Trebo

  11. Dutch Childhood Oncology Group, The Hague, ErasmusMC–Sophia Children's Hospital, Rotterdam, The Netherlands

    M van den Heuvel-Eibrink

  12. Department of Pediatric Hematology/Oncology, Wroclaw, Poland

    D Wójcik

Authors
  1. M Zecca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G Bergamaschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Kratz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Bergsträßer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Danesino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P De Filippi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Hasle
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D Lisini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. F Locatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Pession
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. L Sainati
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J Starý
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M Trebo
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. M van den Heuvel-Eibrink
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. D Wójcik
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. C M Niemeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the European Working Group on MDS in childhood (EWOG-MDS)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zecca, M., Bergamaschi, G., Kratz, C. et al. JAK2 V617F mutation is a rare event in juvenile myelomonocytic leukemia. Leukemia 21, 367–369 (2007). https://doi.org/10.1038/sj.leu.2404484

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404484

This article is cited by

Search

Advanced search

Quick links