but Not Mutations Are Associated with an Overexpression of Retinoid X Receptor Alpha in Essential Thrombocythemia

Essential thrombocythemia (ET) is a blood cancer caused by mutations in and . It is widely recognized that both mutations lead to the constitutive activation of JAK2/STAT signaling, although other JAK/STAT-independent pathogenic mechanisms triggered by these alterations have also been described in ET. In an attempt to study JAK2/STAT-independent mechanisms derived from mutations, our research group created a model with patient-like mutations in calreticulin that lacks JAK counterparts. The introduction of patient-like mutations in the calreticulin of leads to an increase in the transcriptional expression of , independently of JAK2/STAT activation. In the present study, we aim to verify if this mechanism is conserved in patients with ET harboring mutations. To do so, we evaluated the expression of potential orthologs of in human cell lines of interest for the study, as well as in bone marrow (BM) or peripheral blood (PB) mononuclear cells from patients with or mutations. The results revealed that this mechanism is conserved in -mutated ET patients, since , but not mutations, were associated with an overexpression of in patients with ET. The use of drugs targeting the activation or blockade of this target in the analyzed cell lines did not result in changes in cell viability. However, might be relevant in the disease, pointing to the need for future research testing retinoids and other drugs targeting RXRα for the treatment of ET patients.