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.
Highlights
The 2008 World Health Organization (WHO) Classification of Tumors defines refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS‐T) as a provisional entity, with unclassifiable myelodysplastic/myeloproliferative neoplasm (MDS/MPN) status, as opposed to a confirmed entity [1]
An MPL W515L mutation and isolated chromosome 13q deletion is rare in an RARS‐T patient negative for a JAK2 mutation and 5q deletion
A search of the literature reveals a number of studies regarding MPL W515 mutations in MDS with sideroblastic change, it does not reveal any studies on MPL W515 mutations in typical RARS‐T
Summary
The 2008 World Health Organization (WHO) Classification of Tumors defines refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS‐T) as a provisional entity, with unclassifiable myelodysplastic/myeloproliferative neoplasm (MDS/MPN) status, as opposed to a confirmed entity [1]. Previous studies have demonstrated that the MPL W515L mutation is associated with an older age, a lower hemoglobin level and higher platelet counts, the association between the mutation and complications, such as thrombosis, is not clear [8,9]. The current report presents the case of an RARS‐T patient positive for the MPL W515L mutation, but negative for the JAK2 V617F mutation. The patient's prior CBC, from September 2010, demonstrated similar macrocytic anemia (hemoglobin, 9.5 g/dl; MCV, 102 fl) and thrombocytosis (platelet count, 701x109/l), the patient had not been referred for hematological evaluation at that time. From November 2012 until the writing of this study, the patient's hemoglobin concentration (range, 8.0‐10.0 g/dl) and platelet count (range, 600‐770x109/l) have remained stable. A repeat bone marrow biopsy in June 2013 revealed stable hematological results and no evidence of disease progression
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