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JAK2 seems to be a typical cooperating mutation in therapy-related t(8;21)/ AML1-ETO-positive AML

Leukemia volume 21, pages 183–184 (2007)Cite this article

The somatic V617F point mutation, which activates the hematopoietic growth factor receptor-associated JAK2 tyrosine kinase, not only shows a high incidence in the BCR-ABL-negative chronic myeloproliferative disorders but also occurs in lower frequencies in other myeloid malignancies such as myelodysplastic syndrome (MDS) (in around 5% of all cases) or acute myeloid leukemia (AML) with overall incidences between 0.5 and 8% of all cases.1, 2, 3 The distribution of the JAK2 mutations in the diverse cytogenetic and molecular subgroups of AML is not yet clarified. In the study of Lee et al.,1 JAK2 mutations were found in only 3/113 patients leading to an incidence of 2.7%. They were represented in two of three cases by the classical V617F mutation, in one case by a K607N mutation. Both cases with a V617F were diagnosed as AML with the prognostically favorable reciprocal translocation t(8;21)(q22;q22)/AML1-ETO.1

Based on these findings, we analyzed the JAK2 mutation status in 24 consecutive patients with AML with t(8;21)/AML1-ETO. Of these, 20 cases were diagnosed as untreated de novo AML, three cases showed therapy-associated AML (t-AML) after previous malignancies (two after treatment of breast cancer and one after seminoma) whereas one case had relapse of de novo AML. All cases underwent investigation by cytomorphologic evaluation in accordance with the FAB/WHO classification, cytogenetic analysis, interphase fluorescence in situ hybridization and molecular testing for the AML1-ETO gene fusion and JAK2 mutation as reported before.3 A V617F mutation was found in two of the 24 cases (8%). Interestingly, both mutated cases were therapy-related after chemotherapy including antracyclines (AC: doxorubicin and cyclophosphamide) and topoisomerase inhibitors (PEB: cisplatin, ectoposide, bleomycin), respectively. The first patient was a 72-year-old woman with AML M1 5 years after breast cancer (peripheral leukocytes: 12 G/L; hemoglobin: 6.0 g/dL, thrombocytes: 60 G/L). The second patient was a 40-year-old male with AML M2 6 years after testicular seminoma (peripheral leukocytes: 16.3 G/L; hemoglobin: 8.4 g/dl; thrombocytes: 31 G/L). Thus, two of three cases with t-AML t(8;21)/AML1-ETO were JAK2 mutated in contrast to the 21 de novo patients who were all negative for the JAK2 mutation. These data for the first time suggest that JAK2 may be a typical additional aberration in AML with therapy-related t(8;21)/AML1-ETO after treatment with antracyclines and topoisomerase inhibitors.

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Authors and Affiliations

  1. MLL–Munich Leukemia Laboratory, Max-Lebsche-Platz 31, Munich, Germany

    S Schnittger, W Kern, C Haferlach & T Haferlach

  2. Department of Clinical Chemistry, University Hospital of Munich, Grosshadern, Munich, Germany

    U Bacher

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  1. S Schnittger
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Correspondence to S Schnittger.

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Schnittger, S., Bacher, U., Kern, W. et al. JAK2 seems to be a typical cooperating mutation in therapy-related t(8;21)/ AML1-ETO-positive AML. Leukemia 21, 183–184 (2007). https://doi.org/10.1038/sj.leu.2404465

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