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JAK2-V617F activating mutation in acute myeloid leukemia: prognostic impact and association with other molecular markers

Leukemia volume 21, pages 2386–2390 (2007)Cite this article

A Corrigendum to this article was published on 21 November 2007

Characterization of genetic aberrations in acute myeloid leukemia (AML) has substantially improved our understanding of the pathogenesis of this disease and is of growing importance for more efficient risk assessment for individual patients; however, despite relevant advances, the relapse risk for these patients is high.1 Effective risk stratification is especially difficult for patients with normal karyotype, who constitute the single largest cytogenetic group of AML. The presence or absence of mutations in the FLT3, MLL, CEBPA and NPM1 genes and/or overexpression of WT1, BAALC or EVI1 are useful markers to predict the clinical outcome of the subgroup with normal cytogenetics, and some of these markers provide potential targets for molecular therapies. However, more studies are necessary to predict the risk in individual patients.

The activating V617F mutation of JAK2 tyrosine kinase has been detected in the majority of patients with polycythemia vera, and in a significant proportion of patients with essential thrombocythemia and idiopathic myelofibrosis,2 all disorders that can evolve into AML. The same mutation was also found in a small number of patients with either AML or myelodysplastic syndrome (MDS). At present, analysis of patients with AML has identified JAK2-V617F mutations in 51 cases (4.7%), 27 of whom had a preceding myeloproliferative disorder (MPD).3, 4, 5, 6, 7, 8, 9, 10, 11, 12 However, apart from the group of AML with pre-existing MPD, where the incidence seems to be higher than 60% (27/41), there are few data concerning the frequency of JAK2-V617F in specific subtypes of AML and its association with other biological parameters, since only four articles include the characteristics of the total patient cohort analyzed.5, 7, 8, 9 Moreover, whether they influence prognosis in patients with AML has not been determined. To further clarify the biological and prognostic impact of the activating tyrosine kinase JAK2 mutation V617F in AML, we investigated its prevalence in a large number of well-characterized AML patients, correlated the results to French–American–British (FAB) classification and WHO (World Health Organization) diagnostic classification, cytogenetics and other molecular markers, and studied the prognostic relevance of this mutation.

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Acknowledgements

This work was supported by the Fundación Científica de la Asociación Española contra el Cáncer, Ministerio de Educación y Ciencia (SAF2005/06425), ISCIII-RETIC RD06/0020 and Fundación para la Investigación Médica Aplicada y UTE (Spain). We thank María J Larrayoz for technical assistance, José L Vizmanos for useful discussion and Marta García-Granero for statistical support.

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Authors and Affiliations

  1. Division of Oncology, Laboratory of Genetics, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain

    C Vicente, I Vázquez, N Marcotegui, A Conchillo, C Carranza, G Rivell, E Bandrés, I Cristobal, I Lahortiga & M D Odero

  2. Department of Genetics, School of Sciences, University of Navarra, Pamplona, Spain

    C Vicente, I Vázquez, M J Calasanz & M D Odero

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  1. C Vicente
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Correspondence to M D Odero.

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Institution where work was done: Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain

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Vicente, C., Vázquez, I., Marcotegui, N. et al. JAK2-V617F activating mutation in acute myeloid leukemia: prognostic impact and association with other molecular markers. Leukemia 21, 2386–2390 (2007). https://doi.org/10.1038/sj.leu.2404812

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