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Pathological and genomic features of myeloproliferative neoplasms associated with splanchnic vein thrombosis in a single-center cohort

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Abstract

Here, we reviewed clinical-morphological data and investigated mutational profiles by NGS in a single-center series of 58 consecutive MPN-SVT patients admitted to our hospital between January 1979 and November 2021. We identified 15.5% of PV, 13.8% of ET, 34.5% of PMF, 8.6% of SMF and 27.6% of MPN-U. Most cases (84.5%) carried JAK2V617F mutation, while seven patients were characterized by other molecular markers, namely MPL in four and CALR mutations in three cases. NGS was performed in 54 (93.1%) cases: the most frequent additional mutations were found in TET2 (27.8%) and DNMT3A (16.7%) genes, whereas 25 (46.3%) patients had no additional mutation. Cases with JAK2V617F homozygosity had a higher median number of additional mutations than those with low allele burden. More importantly, all cases of leukemic evolution were characterized by a higher median number of co-mutations, and a co-mutational pattern of high-risk lesions, such as truncating mutations of ASXL1, bi-allelic TP53 loss, and CSMD1 mutations. Nevertheless, no difference was found between cases with and without additional somatic mutations regarding fibrotic progression, SVT recurrence, other thrombo-hemorrhagic complications, or death. After a median follow-up of 7.1 years, ten deaths were recorded; fibrotic progression/leukemic evolution was ascertained in one (1.7%) and six (10.3%) patients, respectively, while 22 (37.9%) patients suffered from recurrent thrombosis. In conclusion, our data underline the importance of using NGS analysis in the management of MPN-related SVT as it can support the MPN diagnosis, particularly in “triple-negative” cases, and provide additional information with potential consequences on prognosis and therapeutic strategies.

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Data Availability

The data that support the findings of this study are available from the senior authors upon reasonable request.

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Acknowledgements

This study was partially funded by Italian Ministry of Health—Current research IRCCS to NB. NB is recipient of an Investigator grant from the Associazione Italiana Ricerca sul Cancro (AIRC IG n. 25739).

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Authors and Affiliations

  1. Hematology Division, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy

    Daniele Cattaneo, Cristina Bucelli, Alfredo Marchetti, Marta Lionetti, Elisa Fermo, Valentina Bellani, Claudio De Magistris, Akihiro Maeda, Alessio Marella, Niccolò Bolli & Alessandra Iurlo

  2. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    Daniele Cattaneo, Alfredo Marchetti, Marta Lionetti, Valentina Bellani, Claudio De Magistris, Akihiro Maeda, Alessio Marella & Niccolò Bolli

  3. Gastroenterology and Hepatology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Massimo Primignani

  4. Epidemiology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Dario Consonni

  5. Division of Pathology, ASST Santi Paolo e Carlo, San Paolo Hospital, Milan, Italy

    Umberto Gianelli

  6. Department of Health Sciences, University of Milan, Milan, Italy

    Umberto Gianelli

  7. Scientific Directorate, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy

    Antonino Neri

  8. University of Milan, Milan, Italy

    Luca Baldini

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  1. Daniele Cattaneo
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  2. Cristina Bucelli
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Contributions

D. Cattaneo, N. Bolli, and A. Iurlo were responsible for study concept and design and wrote the paper. D. Consonni was responsible for statistical analyses. A. Marchetti, M. Lionetti, E. Fermo, A. Maeda, A. Marella, A. Neri, and N. Bolli made and interpreted mutational analyses. U. Gianelli reviewed bone marrow biopsies. D. Cattaneo, C. Bucelli, V. Bellani, C. De Magistris, M. Primignani, L. Baldini, and A. Iurlo followed the patients and collected data. All authors critically reviewed and approved the final version of the manuscript.

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Correspondence to Daniele Cattaneo.

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Niccolò Bolli and Alessandra Iurlo co-contributing senior authors.

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277_2023_5217_Fig5_ESM.png

Supplementary Fig. S4 VAF mutation study with flanking CIs in our patient cohort. VAF was modeled according to a binomial distribution. (PNG 234 kb)

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Cattaneo, D., Bucelli, C., Marchetti, A. et al. Pathological and genomic features of myeloproliferative neoplasms associated with splanchnic vein thrombosis in a single-center cohort. Ann Hematol 102, 1409–1420 (2023). https://doi.org/10.1007/s00277-023-05217-2

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