MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms

Abstract

Objective: The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K) were described in patients with essential thrombocythemia (ET) and primary (idiopathic) myelofibrosis (PMF). The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. Materials and Methods: A total of 77 patients (66 were diagnosed with ET and 11 with PMF) and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction.Results: In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66) and 6 had PMF (54.5%, 6/11). In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively), had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies.Conclusion: MPL W515L/K mutations may be helpful for identifying clonal disease in MPN patients with no established Ph chromosome or JAK-2 V617F mutation.Conflict of interest:None declared.

The mutation profile of JAK2, MPL and CALR in Mexican patients with Philadelphia chromosome-negative myeloproliferative neoplasms

“…ET = essential thrombocythemia; PV = polycythemia vera; MF = myelofibrosis; NI: Not investigated; NS: Not specified. and lower leukocyte and hemoglobin values in CALR mutant patients compared to those with JAK2V617F or MPL mutations [21][22][23][24][25][27] In our cohort, we were not able to find any significant difference for hemoglobin or platelet count, but significantly…”

Essential thrombocythemia withMpl W515 Kmutation in a child presenting with Budd–Chiari syndrome

“…Mpl mutations, including W515K/L/A/R and S505N, occur in about 2-6% of patients with ET, resulting in receptor hyperactivity or isolated thrombocytosis [12,20,21]. Mpl W515 L and K mutations cause cytokine-independent growth and TPO hypersensitivity, activating the JAK-STAT/ERK/Akt signal pathways [11]. Other Mpl mutations (Mpl W515S, W5151A, and Mpl S505N) have also been reported in cases of hereditary thrombocytosis [7].…”

“…These acquired JAK2 and Mpl gain of function mutations are extremely rare in children [10]. The most frequent in children is the W515L and W515K Mpl mutations that result in constitutive activation of the JAK2-STAT pathway after activation of the Mpl receptor by thrombopoietin (TPO) [11][12][13].…”

Genetic analysis of BCR-ABL negative chronic myeloproliferative diseases at initial diagnosis and their clinical effects

“…CALR mutation is the second common mutation in ET without JAK2 V617F which is reported in about 40-50%. MPL mutation is positive 5% in ET without JAK2 V617F 7,[13][14][15] . Our data were compatible with the literature.…”