Clonal Progression and Leukemic Transformation of a TP53 Mutated Post-Polycythaemia Vera Myelofibrosis

Previous studies investigating the role of TP53 mutations in chronic phase MPN have yielded inconsistent results. As such, the clinical relevance of these mutations remains to be elucidated. We report a case of a 67-year-old woman with a leukemic transformation of a post-polycythaemia vera myelofibrosis (post-PV MF) that culminated in the rare development of a myeloid sarcoma. During a 4-year follow-up, the patient had a stable JAK2 Val617Phe and NFE2 mutation (Variant Allele Frequencies (VAF's) 85%-87% and 43%-50%, respectively) and low-burden TP53 mutation (VAF 2%-7%) in blood and bone marrow. Despite having a low-risk post-PV MF, the patient soon presented with an aggressive lytic lesion in the humerus, which proved to be a myeloid sarcoma. The sarcoma was positive for JAK2 Val617Phe but, interestingly, was also highly enriched for the TP53 mutation (VAF 81%), implicating a role of the TP53 mutation in the leukemic progression. This case provides molecular evidence that a TP53 mutation, even at a low burden, may contribute to leukemic progression of a chronic phase myeloproliferative neoplasm (MPN). These observations increase our understanding of the pathophysiologic behavior of TP53 mutations and underscore the importance of further causal research towards the clinical implications of these mutations in chronic phase MPN.