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ASCO 2026 | How may the timing of TP53 mutation acquisition impact outcomes in patients with MPNs?
The negative association between TP53 mutations and clinical outcomes in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) has been widely studied; however, the impact of these aberrations in myeloproliferative neoplasms (MPNs) has not been widely studied. In this interview, Akriti Jain, MD, Cleveland Clinic, Cleveland, Ohio, discusses the prognostic implications of the timing of TP53 mutation acquisition in MPNs and MDS/MPN overlap syndromes, highlighting that later emergence of the mutation in the disease course is associated with significantly poorer survival outcomes. Dr Jain emphasizes the potential importance of considering the timing of TP53 acquisition for improved risk stratification and clinical decision-making. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Yes, thank you for that excellent question. The timing of TP53 acquisition in MDS and MPNs carries an important prognostic implication. We know TP53 mutation is of a bad prognosis in MDS and AML, but its impact in MPN is not as widely studied or known. So more than just whether having the TP53 mutation affects the prognosis, we wanted to study whether the timing of TP53 acquisition has important prognostic implications...
Yes, thank you for that excellent question. The timing of TP53 acquisition in MDS and MPNs carries an important prognostic implication. We know TP53 mutation is of a bad prognosis in MDS and AML, but its impact in MPN is not as widely studied or known. So more than just whether having the TP53 mutation affects the prognosis, we wanted to study whether the timing of TP53 acquisition has important prognostic implications. And we saw that the later emergence of the mutation is associated with significantly worse survival outcomes. We’re presenting the study at the 2026 ASCO meeting. It’s a poster that will be presented on Monday by my brilliant fellow, Dr. Granat. And we basically show that the detection of TP53 and its timing may provide a clinically meaningful risk stratification beyond the patient’s age and the presence of TP53 mutation alone. And like I said, survival analysis demonstrated that later acquisition was associated with poorer outcomes. The important part here is that we looked at survival not from the time of diagnosis of MPN, but from the time of acquisition of the TP53 mutation. And hence, we saw that if someone acquired the TP53 mutation later in the course of disease, their prognosis was worse compared to someone that had the TP53 mutation at diagnosis. We don’t have currently any FDA-approved drugs to specifically target TP53. There have been drugs in the past that have been studied in Phase II studies, but haven’t made it to Phase III studies yet. And this is an important implication because if the acquisition of TP53 has adverse prognosis as shown by our study, this can help guide conversations between patients and physicians, especially the important conversation of when to consider an allogeneic stem cell transplant, which becomes all the more important for someone who is a candidate if they have a TP53 mutation.
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