MPL W515L mutation in patients with myeloproliferative diseases

Abstract

18019 Background: The BCR-ABL negative chronic myeloproliferative disorders (MPD) include polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis with idopathic myelofibrosis (IMF). Although clonal hematopoiesis was observed in these disorders more than three decades ago, the molecular etiology of these disorders was not known until recently when several groups reported a somatic mutation in the JAK2 tyrosine kinase (JAK2 V617F) in most patients with PV and in a subset of patients with ET and IMF. As JAK2 V617F, MPL W515L is a novel acquired mutation that induces constitutive cytokine-independent activation of the JAK-STAT pathway in MPD. The discovery of this mutation provides a novel mechanism for activation of signal transduction in hematopoietic malignancies. Methods: To investigate its prevalence in Chinese patients with MPD, we introduced allele-specific PCR (AS- PCR) combined with sequence analysis to simultaneously screen MPL W515L and JAK2 V617F mutations in 190 MPD patients. Results: The results indicated that MPL W515L mutation was found to be harbored in only one of 102 ET patients (1.0%) and was not detected in PV, IMF, chronic myelogenous leukemia (CML) patients. Sixty eight BCR/ABL-negative MPD patients (46.3%) were found harbouring JAK2 V617F mutation (PV, 62.5% ET, 42.1% IMF 38.1%). Furthermore, MPL W515L and JAK2 V617F mutations were not detected in patients of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS) and CML. Conclusions: MPL W515L mutations may contribute to the primary molecular pathogenesis mechanism of Chinese patients with ET. No significant financial relationships to disclose.