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Chronic myeloproliferative neoplasms

Platelet count predicts driver mutations’ co-occurrence in low JAK2 mutated essential thrombocythemia and myelofibrosis

Leukemia volume 35, pages 1490–1493 (2021)Cite this article

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Essential thrombocythemia (ET) and primary myelofibrosis (primary MF, PMF) are Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) [1]. About 90% of cases show a clonal driver gene mutation among JAK2V617F (50–60%), CALR exon 9 (20–25%), or MPL exon 10 (3–15%) [2,3,4].

The three MPNs driver gene mutations were originally described as mutually exclusive. Therefore, finding a JAK2 mutation eludes further diagnostic molecular investigations, except for those centers that routinely perform next generation sequencing (NGS). Of note, the most recent World Health Organization (WHO) classification indicates searching for additional myeloid gene variants in MPNs only if the three major clonal mutations are absent [1]. Besides, current European guidelines indicate JAK2 as the first test in suspected ET/MF and, only in the case of JAK2 negativity, studying CALR and MPL status [5]. As for ET, NGS analysis at diagnosis is not recommended [5, 6]. On the contrary, in MF an extensive molecular characterization has substantially enhanced prognostic assessment, especially with regard to stem cell transplant decision [7, 8]. Focusing on common practice, testing all ET and MF patients by NGS would be also limited by its practical availability and by financial implications.

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Fig. 1: Thirty genes-panel DNA sequence variants in 47 patients with essential thrombocythemia and primary myelofibrosis and a low JAK2 allele burden according to double/single mutated status.

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Acknowledgements

This work was supported, as for the Varese Group, by grants of the Fondazione Regionale Ricerca Biomedica, Milan, Italy [FRRB project no. 2015-0042, Genomic profiling of rare hematologic malignancies, development of personalized medicine strategies, and their implementation into the Rete Ematologica Lombarda (REL) clinical network]; by grants from the Ministero della Salute, Rome, Italy [Finalizzata 2018, NET-2018-12365935, Personalized medicine program on myeloid neoplasms: characterization of the patient’s genome for clinical decision making and systematic collection of real world data to improve quality of health care], by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca, Roma, Italy [PRIN 2017, 2017WXR7ZT; Myeloid Neoplasms: an integrated clinical, molecular and therapeutic approach], by grants from Fondazione Matarelli, Milan, Italy and AIL-Varese ONLUS, Varese, Italy.

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Authors and Affiliations

  1. Hematology, ASST Sette Laghi, Ospedale di Circolo, Varese, Italy

    Barbara Mora, Margherita Maffioli, Daniela Barraco, Michele Merli & Francesco Passamonti

  2. Cytogenetics and Medical Genetics Laboratory, ASST Sette Laghi, Ospedale di Circolo, Varese, Italy

    Claudia Siracusa, Raffaella Accetta, Laura Libera, Francesco Pallotti & Rosario Casalone

  3. Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Elisa Rumi, Ilaria Carola Casetti, Daniela Pietra & Luca Arcaini

  4. Department of Molecular Medicine, University of Pavia, Pavia, Italy

    Elisa Rumi, Ilaria Carola Casetti, Chiara Trotti & Luca Arcaini

  5. Cancer Center, IRCCS Humanitas Research Hospital & Humanitas University, Rozzano, Italy

    Marianna Rossi, Marta Ubezio & Matteo Giovanni Della Porta

  6. Pathology, ASST Sette Laghi, Ospedale di Circolo, Varese, Italy

    Silvia Uccella

  7. Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Silvia Uccella, Francesco Pallotti, Lorenza Bertù & Francesco Passamonti

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  1. Barbara Mora
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Correspondence to Francesco Passamonti.

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Mora, B., Siracusa, C., Rumi, E. et al. Platelet count predicts driver mutations’ co-occurrence in low JAK2 mutated essential thrombocythemia and myelofibrosis. Leukemia 35, 1490–1493 (2021). https://doi.org/10.1038/s41375-020-01053-9

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