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SOHO 2025 | Uncovering the molecular determinants of MPN progression
In this interview, Francesco Passamonti, MD, University of Milan, Milan, Italy, discusses the use of next-generation sequencing (NGS) to identify molecular determinants of progression in myeloproliferative neoplasms (MPNs), highlighting the relevance of several mutations in patients with primary or secondary myelofibrosis (MF). Dr Passamonti suggests that information about these genetic predictors of outcomes should be utilized in clinical practice to guide the treatment of patients. This interview took place at the 13th Annual Meeting of the Society of Hematologic Oncology (SOHO 2025) in Houston, TX.
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Transcript
With the wide use of NGS in myeloid neoplasms, we discovered that some of these variants may be relevant also in myeloproliferative neoplasms. And we know that half of the patients with polycythemia vera can have additional myeloid variants beside the classical driver mutations, JAK2, CALR, and MPL. And these mutations may have an impact on overall survival, evolution into acute leukemia, and the MF transformation...
With the wide use of NGS in myeloid neoplasms, we discovered that some of these variants may be relevant also in myeloproliferative neoplasms. And we know that half of the patients with polycythemia vera can have additional myeloid variants beside the classical driver mutations, JAK2, CALR, and MPL. And these mutations may have an impact on overall survival, evolution into acute leukemia, and the MF transformation. And these genes are ASXL1, SRSF2, IDH1/2, EZH2, and NFE2. So on the basis of these genes, we can define and align the future evolution and modification of the disease.
Concerning primary myelofibrosis, we currently use ASXL1, the EZH2, IDH1 and 2, and SRSF1 for the classification and prognosis of patients with myelofibrosis according to the MIPSS70. But most recently, we have additional information about the potential and difficult role of ASXL1 – probably it’s not relevant per se but just addicted to other mutations or it is more relevant the VAF of this gene in respect to having the gene mutated yes or no. And also TP53 in the multi-allelic constellation may be quite relevant and also RAS, symbol mutation especially in the prediction of response to JAK inhibitors, and finally also U2AF1.
And concerning the post-PV and post-ET myelofibrosis, we have very recently understood that having ASXL1 or having U2AF1 and the TP53 or SRSF2 may be quite relevant for the prognostication. And so I think that now we have information about the predictors of outcome, the genetic predictors of outcome in MPN, and we have to use this information for guiding the treatment of our patients.
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