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Updated: Jun 25, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
MPLW515L mutation in acute megakaryoblastic leukaemia
K Hussein1, O Bock, K Theophile
1Institute of Pathology, Hannover Medical School, Hannover, Germany.
Abstract:
The thrombopoietin receptor gene (MPL) is expressed in megakaryocytes and exhibits the gain of function point mutation W515K/L in approximately 5% of patients with primary myelofibrosis/idiopathic myelofibrosis (PMF) representing one subtype of the chronic myeloproliferative disorders (myeloproliferative neoplasm). A series of primary and secondary acute myeloid leukaemias (AML) with megakaryoblastic phenotype and myelofibrosis unrelated to PMF (n=12) was analysed for the MPL(W515K/L) mutation by pyrosequencing. In three cases (25%), MPL(W515L) was found and in two of these a combination with trisomy 21 or the Philadelphia chromosome occurred. None of the secondary AML cases evolving from pre-existing PMF showed MPL(W515K/L) (n=4). We conclude that MPL(W515L) occurs in a considerable proportion of acute megakaryoblastic leukaemias with myelofibrosis unrelated to PMF.
Insights
The MPL W515L mutation is found in 25% of acute myeloid leukemias with megakaryoblastic features and myelofibrosis. This finding is significant for acute myeloid leukemia (AML) subtypes unrelated to primary myelofibrosis (PMF).
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- The thrombopoietin receptor gene (MPL) mutations, specifically W515K/L, are implicated in myeloproliferative neoplasms like primary myelofibrosis (PMF).
- MPL mutations represent a key driver in a subset of chronic myeloproliferative disorders.
Purpose of the Study:
- To investigate the frequency of the MPL W515K/L mutation in acute myeloid leukemias (AML) with a megakaryoblastic phenotype and myelofibrosis.
- To determine if this mutation is associated with AML subtypes independent of PMF.
Main Methods:
- Analysis of 12 cases of primary and secondary AML with megakaryoblastic phenotype and myelofibrosis.
- Utilizing pyrosequencing to detect the MPL W515K/L mutation.
Main Results:
- The MPL W515L mutation was identified in 3 out of 12 cases (25%) of AML with megakaryoblastic features and myelofibrosis.
- In two of these positive cases, the mutation co-occurred with trisomy 21 or the Philadelphia chromosome.
- No MPL W515K/L mutations were detected in secondary AML cases evolving from pre-existing PMF (n=4).
Conclusions:
- The MPL W515L mutation is present in a significant proportion of acute megakaryoblastic leukemias with myelofibrosis that are unrelated to PMF.
- This suggests MPL W515L as a potential diagnostic or prognostic marker in this specific AML subgroup.
