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Molecular profile of CD34+ stem/progenitor cells according to JAK2V617F mutation status in essential thrombocythemia

Leukemia volume 23, pages 997–1000 (2009)Cite this article

Essential thrombocythemia (ET) is mainly characterized by the abnormal proliferation of a malignant megakaryocytic clone and by persistent thrombocytosis. Recently, a JAK2 mutation (JAK2V617F) has been reported in ET and other myeloproliferative neoplasms. In particular, 40–60% of ET patients harbor this mutation and a substantial proportion of them are heterozygous with allele burden below 50%.1 JAK2V617F mutation distinguishes the disease into two biologically distinct subtypes with the V617F-positive subgroup exhibiting many laboratory and clinical similarities to polycythemia vera. Furthermore, 50 patients with V617F-negative ET remained V617F-negative for more than 6 years, indicating that this disorder is distinct from, and not an early ‘pre-JAK2’ phase of V617F-positive ET.2

Despite this finding, the molecular pathology of ET according to the presence or the absence of JAK2V617F mutation is still unknown. Gene expression profiling of granulocytes from ET patients showed that patients lacking the mutation do not display constitutively active JAK–STAT signaling and show significantly lower expression of the target genes Pim1 and SOCS2.3 More recently, we read with interest the study by Puigdecanet et al.,4 which compared the gene expression profile of two groups of ET, selected for presence or absence of JAK2V617F mutation in granulocytes. A supervised hierarchical clustering analysis on differentially expressed genes showed a classification of two main groups of patients, which is independent from JAK2V617F mutation status. However, the authors confirmed that some genes involved in the JAK–STAT signaling pathway (CISH, SOCS2, SOCS3 and PIM1) present lower expression levels in JAK2V617F-negative patients.

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References

  1. Passamonti F, Rumi E, Pietra D, Della Porta MG, Boveri E, Pascutto C et al. Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders. Blood 2006; 107: 3676–3682.

    Article  CAS  Google Scholar 

  2. Campbell PJ, Baxter EJ, Beer PA, Scott LM, Bench AJ, Huntly BJ et al. Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation. Blood 2006; 108: 3548–3555.

    Article  CAS  Google Scholar 

  3. Schwemmers S, Will B, Waller CF, Abdulkarim K, Johansson P, Andreasson B et al. JAK2V617F-negative ET patients do not display constitutively active JAK/STAT signalling. Exp Hematol 2007; 35: 1695–1703.

    Article  CAS  Google Scholar 

  4. Puigdecanet E, Espinet B, Lozano JJ, Sumoy L, Bellosillo B, Arenillas L et al. Gene expression profiling distiguishes JAK2V617F-negative from JAK2V617F-positive patients in essential thrombocythemia. Leukemia 2008; 22: 1368–1376.

    Article  CAS  Google Scholar 

  5. Manfredini R, Zini R, Salati S, Siena M, Tenedini E, Tagliafico E et al. The kinetic status of hematopoietic stem cell (HSC) subpopulations underlies a differential expression of genes involved in self-renewal, commitment and engraftment. Stem Cells 2005; 23: 496–506.

    Article  CAS  Google Scholar 

  6. Kovacs R, Teo S, Buser AS, Brutsche M, Tiedt R, Tichelli A et al. Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of JAK2. Blood 2005; 106: 3374–3376.

    Article  Google Scholar 

  7. Moliterno AR, Williams DM, Rogers O, Isaacs MA, Spivak JL . Phenotypic variability within the JAK2 V617F-positive MPD: roles of progenitor cell and neutrophil allele burdens. Exp Hematol 2008; 36: 1486–1492.

    Article  Google Scholar 

  8. Rumi E, Passamonti F, Pietra D, Della Porta MG, Arcaini L, Boggi S et al. JAK2 (V617F) as an acquired somatic mutation and a secondary genetic event associated with disease progression in familial myeloproliferative disorders. Cancer 2006; 107: 2206–2211.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by Fondi ex 60% of the University of Bologna 2006 (LC), PRIN 2006 (AMV), PRIN 2006 (RM), Programma di ricerca oncologica 2006- Regione Emilia-Romagna (RML), Programma di ricerca Regione-Università 2007–2009 (RML), and by BolognaAIL (Italian association against Leukemia, Bologna section). This paper is dedicated to the memory of Stefano Ferrari, Professor of Biochemistry at University of Modena and Reggio Emilia.

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Authors and Affiliations

  1. Department of Hematology and Oncological Science ‘L& A Seràgnoli’, University of Bologna, Bologna, Italy

    L Catani, D Sollazzo, E Ottaviani, M Baccarani, N Vianelli & R M Lemoli

  2. Department of Biomedical Science, Section of Biological Chemistry, University of Modena and Reggio Emilia, Modena, Italy

    R Zini, S Ferrari & R Manfredini

  3. Department of Hematology, University of Florence, Florence, Italy

    A M Vannucchi

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  1. L Catani
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  2. R Zini
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Correspondence to L Catani.

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Catani, L., Zini, R., Sollazzo, D. et al. Molecular profile of CD34+ stem/progenitor cells according to JAK2V617F mutation status in essential thrombocythemia. Leukemia 23, 997–1000 (2009). https://doi.org/10.1038/leu.2008.357

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