CO58 | Single-cell multi-omics unravels molecular and cellular programs underlying ruxolitinib response in myelofibrosis

Myelofibrosis (MF) is a clonal hematological disease originating by the sequential acquisition of somatic mutations in hematopoietic stem and progenitor cells (HSPC). Alongside so-called “driver mutations” triggering the constitutive activation of JAK-STAT pathway and inducing myeloproliferation, MF may present with additional mutations often affecting epigenetic regulators. The JAK-inhibitor Ruxolitinib (Ruxo) effectively relieves MF symptoms but rarely eradicates the malignant clone, with highly variable responses among patients. Understanding the molecular mechanisms underlying Ruxo heterogeneous efficacy is essential to improve therapeutic strategies.