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Detection of an MPLW515 mutation in a case with features of both essential thrombocythemia and refractory anemia with ringed sideroblasts and thrombocytosis

Leukemia volume 22, pages 453–455 (2008)Cite this article

BCR-ABL-negative chronic myeloproliferative diseases (CMPD) and myelodysplastic syndromes (MDS) are both very heterogeneous and in some cases show cytomorphological and clinical overlaps. This is especially true for the subentities chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia and myelodysplastic/myeloproliferative disease, unclassifiable', which were classified by the WHO as its own category of myelodysplastic/myeloproliferative disorders. Recently, refractory anemia with ringed sideroblasts associated with anemia but marked thrombocytosis >500 × 109/l, and a proportion of at least 15% of ringed sideroblasts in the bone marrow was added as a distinct entity to this category.1, 2, 3, 4, 5 Most cases of RARS-T show a normal karyotype.1, 2, 3, 4, 5 In addition, this specific subtype was reported to have a high frequency of the JAK2 V617F mutation.1, 2, 4 The V617F mutation is primarily associated with the CMPD, being found in nearly all polycythemia vera (PV) and in 50–60% of all essential thrombocytosis (ET) and chronic idiopathic myelofibrosis (CIMF) cases, but was also detected rarely in MDS.6 Therefore, the high frequency of JAK2 V617F in RARS-T emphasizes the ambiguous position of this subentity between CMPD and MDS, as do molecular and cytomorphological aspects. However, the genetic characterization of RARS-T is not complete, as 10–50% of all cases did not show a V617F mutation.

Lately, somatic mutations of the MPL gene with its coding function for the thrombopoietin receptor were detected in ∼5% of CIMF and in ∼1% of all ET. So far, two different variants, the W515L and the W515K mutation, were identified. They are localized in the transmembranous domain and thus might be critical for receptor dimerization. They cause single amino-acid exchanges (tryptophan to leucine or lysine, respectively) and confer constitutive cytokine-independent activation of the JAK–STAT pathway as gain-of-function mutations, similar to the V617F.7, 8 So far, they were not detected in PV, AML, MDS or CMML.7

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Authors and Affiliations

  1. MLL—Munich Leukemia Laboratory, Munich, Germany

    S Schnittger, C Haferlach, W Kern & T Haferlach

  2. Stem Cell Transplantation, University Hospital of Hamburg-Eppendorf, Hamburg, Germany

    U Bacher

  3. Hämatologisch-Onkologische Praxis, Regensburg, Germany

    R Dengler & A Kröber

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  1. S Schnittger
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Correspondence to S Schnittger.

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Schnittger, S., Bacher, U., Haferlach, C. et al. Detection of an MPLW515 mutation in a case with features of both essential thrombocythemia and refractory anemia with ringed sideroblasts and thrombocytosis. Leukemia 22, 453–455 (2008). https://doi.org/10.1038/sj.leu.2404909

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