P983: SINGLE CELL ANALYSIS ALLOWS THE EARLY DETECTION OF LEUKEMIC CLONES IN MPN PATIENTS

Background: Background: Myeloproliferative neoplasms (MPNs) are a group of hematopoietic stem cell disorders resulting in the overproduction of myeloid differentiated cells. Primary Myelofibrosis (PMF) is characterized by the worst prognosis and 15-20% of cases develop secondary Acute Myeloid Leukemia (AML). MPNs driver mutations affect JAK2, CALR or MPL genes. Moreover, mutations in epigenetic regulators can exacerbate the disease and alter response to treatment. Our group recently demonstrated through single cell analysis that MPNs progression is due to increased genetic heterogeneity, loss of heterozygosity and parallel AML evolution. Aims: Aims: In this work we sought to define the genomic architecture of MPN patients during disease evolution, and gain insight into the chromatin and transcriptional perturbations induced by epigenetic modifiers’ mutations. Methods: Methods: In order to describe MPNs clonal hierarchy at the single cell level, we employed Mission Bio Tapestri platform. We analyzed the CD34+ compartment of 3 patients during the chronic phase of the disease and after leukemic transformation through a custom panel comprising 29 genes frequently mutated in myeloid neoplasms. CNV assessment was performed on the same data through Mosaic algorithm. On one single nucleus and ATAC-seq