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:

Presence of polyclonal hematopoiesis in females with Ph-negative myeloproliferative neoplasms

Leukemia volume 29, pages 2432–2434 (2015)Cite this article

Subjects

Classical Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPN) are considered to originate from somatic mutation(s) of a hematopoietic stem cell leading to clonal hematopoiesis, as shown by X-chromosome allelic usage in females. Somatic mutations in JAK2, cMPL and calreticulin (CALR) genes are the three main disease-defining mutations. Mutations in the JAK2 gene are found in almost all polycythemia vera patients and in 45–50% of essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients, while mutations in cMPL are found in about 2–5% of ET and PMF. CALR mutations (CALRMUT) have been identified in the majority of ET and PMF patients who lack JAK2 and cMPL mutations, but are generally not found in PV patients. Compared with JAK2- and cMPL-mutated patients, CALRMUT patients have higher platelet counts, lower hemoglobin and leukocyte counts, a lower risk of thrombosis1 and a more favorable prognosis, but no difference in the rate of transformation to post-ET PMF.2

Determination of clonality based on X-chromosome inactivation has helped to differentiate reactive processes from MPNs. However, prior to the discovery of MPN disease-defining mutations, it was reported that some patients with a clinical phenotype of ET had polyclonal hematopoiesis.3

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

Figure 1
Figure 2

References

  1. Tefferi A, Wassie EA, Lasho TL, Finke C, Belachew AA, Ketterling RP et al. Calreticulin mutations and long-term survival in essential thrombocythemia. Leukemia 2014; 28: 2300–2303.

    Article  CAS  Google Scholar 

  2. Tefferi A, Barbui T . Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management. Am J Hematol 2015; 90: 162–173.

    Article  CAS  Google Scholar 

  3. Harrison CN, Gale RE, Machin SJ, Linch DC . A large proportion of patients with a diagnosis of essential thrombocythemia do not have a clonal disorder and may be at lower risk of thrombotic complications. Blood 1999; 93: 417–424.

    CAS  PubMed  Google Scholar 

  4. Busque L, Zhu J, DeHart D, Griffith B, Willman C, Carroll R et al. An expression based clonality assay at the human androgen receptor locus (HUMARA) on chromosome X. Nucleic Acids Res 1994; 22: 697–698.

    Article  CAS  Google Scholar 

  5. Prchal JT, Guan YL . A novel clonality assay based on transcriptional analysis of the active X chromosome. Stem Cells 1993; 11: 62–65.

    Article  Google Scholar 

  6. Swierczek SI, Piterkova L, Jelinek J, Agarwal N, Hammoud S, Wilson A et al. Methylation of AR locus does not always reflect X chromosome inactivation state. Blood 2012; 119: e100–e109.

    Article  CAS  Google Scholar 

  7. Allen C, Lambert JR, Linch DC, Gale RE . X chromosome inactivation analysis reveals a difference in the biology of ET patients with JAK2 and CALR mutations. Blood 2014; 124: 2091–2093.

    Article  CAS  Google Scholar 

  8. Nussenzveig RH, Swierczek SI, Jelinek J, Gaikwad A, Liu E, Verstovsek S et al. Polycythemia vera is not initiated by JAK2V617F mutation. Exp Hematol 2007; 35: 32–38.

    Article  CAS  Google Scholar 

  9. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013; 369: 2379–2390.

    Article  CAS  Google Scholar 

  10. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013; 369: 2391–2405.

    Article  CAS  Google Scholar 

  11. Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, Milosevic JD et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 2014; 123: 1544–1551.

    Article  CAS  Google Scholar 

  12. Swierczek SI, Agarwal N, Nussenzveig RH, Rothstein G, Wilson A, Artz A et al. Hematopoiesis is not clonal in healthy elderly women. Blood 2008; 112: 3186–3193.

    Article  CAS  Google Scholar 

  13. Jones AV, Ward D, Lyon M, Leung W, Callaway A, Chase A et al. Evaluation of methods to detect CALR mutations in myeloproliferative neoplasms. Leuk Res 2015; 39: 82–87.

    Article  CAS  Google Scholar 

  14. Rumi E, Harutyunyan AS, Pietra D, Milosevic JD, Casetti IC, Bellini M et al. CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis. Blood 2014; 123: 2416–2419.

    Article  CAS  Google Scholar 

  15. Stein BL, Williams DM, Rogers O, Isaacs MA, Spivak JL, Moliterno AR . Disease burden at the progenitor level is a feature of primary myelofibrosis: a multivariable analysis of 164 JAK2 V617F-positive myeloproliferative neoplasm patients. Exp Hematol 2011; 39: 95–101.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Myeloproliferative Disorders (MPD) Consortium (Project #1; JTP Principal Investigator) research funding from the National Institutes of Health (Grant number: NIH-P01CA108671). LTL is supported by a doctoral fellowship from the CAPES Foundation, Ministry of Education of Brazil, Brasília – DF 70040-020, Brazil.

Author information

Author notes

  1. S Swierczek and L T Lima: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology, Internal Medicine Department, University of Utah and VAH, Salt Lake City, UT, USA

    S Swierczek, L T Lima, T Tashi, S J Kim & J T Prchal

  2. Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil

    L T Lima

  3. Utah Cancer Specialists, Salt Lake City, UT, USA

    X T Gregg

  4. Department of Hematopathology, ARUP Laboratories, Salt Lake City, UT, USA

    J T Prchal

Authors
  1. S Swierczek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L T Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Tashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S J Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. X T Gregg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J T Prchal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J T Prchal.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Swierczek, S., Lima, L., Tashi, T. et al. Presence of polyclonal hematopoiesis in females with Ph-negative myeloproliferative neoplasms. Leukemia 29, 2432–2434 (2015). https://doi.org/10.1038/leu.2015.249

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2015.249

Search

Advanced search

Quick links