Single-Cell Multi-Omics Reveals the Genetic, Cellular and Molecular Landscape of TP53Mutated Leukemic Transformation in MPN

In myeloid malignancies, presence of ‘multi-hit’ TP53mutations is associated with lack of response to conventional therapy and dismal outcomes, particularly when found in combination with a complex karyotype. Therefore, it is crucial to understand the biological basis of TP53-mutant driven clonal evolution, suppression of antecedent clones and eventual disease transformation to inform the development of more effective therapies. Myeloproliferative neoplasms (MPN) represent an ideal tractable disease model to study this process, as progression to secondary acute myeloid leukemia (sAML) frequently occurs through the acquisition of TP53missense mutations.