An MPL W515L mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis: A case report

Abstract

The current study presents the case of a 63-year-old patient exhibiting refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), who was positive for the MPL W515L mutation, but negative for the JAK2 V617F mutation. Following diagnosis, the patient remained asymptomatic for over three years, however, in August 2012, the patient relapsed and was administered with supportive treatment in the form of subcutaneous darbepoetin α at a dose of 300 μg/week, which resulted in an increased hemoglobin concentration, allowing the patient to remain transfusion-independent. The MPL W515L mutation has been reported in two previous cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with ringed sideroblasts, however, to the best of our knowledge, the current report is the first to present a case of RARS-T with an MPL W515L mutation. A clinical trial designed to evaluate the efficacy of a targeted agent against the JAK2 V617F mutation is currently ongoing, with the aim of providing a novel therapeutic strategy for treating MDS/MPN patients. As MPL is located upstream of the JAK-STAT signaling pathway, it is a possible therapeutic target in MDS/MPN patients positive for an MPL W515L mutation, but negative for a JAK2 V617F mutation.

Clinical, genomic, and transcriptomic differences between myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN‐RS‐T) and myelodysplastic syndrome with ring sideroblasts (MDS‐RS)

“…2 Next-generation sequencing (NGS) has identified recurrent somatic mutations in SF3B1, JAK2, and other genes providing further evidence of the clonal nature of this disease. 3,4 Despite clinical, histological, and molecular similarities with MDS with ring sideroblasts (MDS-RS), 5 the clinical outcomes of these entities are different. Although the presence of SF3B1 mutations in the context of >15% bone marrow ring sideroblasts supports the diagnosis of MDS/MPN-RS-T, the degree of thrombocytosis is variable, and the current diagnostic cutoff for RS percentage and platelet count leads to diagnostic challenges and might not be reflective of underlying disease biology.…”