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MPL
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Interpretation 2
Tier 1
MPL
Variants
MPL codon(s) 515 missense
MPL W515L
MPL W515K
Primary Sites
Blood
Bone Marrow
Tumor Types
Myeloproliferative Neoplasm
Essential Thrombocythemia
Primary Myelofibrosis
Acute Leukemia of Unspecified Cell Type
Acute Myeloid Leukemia
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Cytopenia
Eosinophilia
Histiocytic and Dendritic Cell Neoplasms
Langerhans Cell Histiocytosis
Leukocytosis
Leukopenia
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Monocytosis
Myelodysplastic Syndrome
Myelodysplastic/Myeloproliferative Neoplasm
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
T Lymphoblastic Leukemia/Lymphoma
Thrombocytopenia, Unspecified
Thrombocytosis
Interpretation

MPL encodes the thrombopoietin receptor, an important growth and survival factor for megakaryocytes. Somatic activating mutation in MPL (W515L, W515K) has been reported in approximately 1%-10% of cases of JAK2 V617F-negative myelofibrosis, essential thrombocythemia, a subset of cases of acute megakaryoblastic leukemia and has been associated with sensitivity to JAK inhibitors. The W515 mutations are typically not observed in polycythemia vera or other myeloid disorders (chronic myelomonocytic leukemia, myelodysplastic syndrome). A S505N activating mutation has also been described in familial essential thrombocythemia. MPL mutation is included as one of the major diagnostic criteria for primary myelofibrosis and essential thrombocythemia in the 2016 revision of the WHO classification.

Citations
  1. Pikman Y, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006;3(7):e270
  2. Ding J, et al. Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood 2004;103(11):4198-200
  3. Pardanani AD, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006;108(10):3472-6
  4. Hussein K, et al. MPLW515L mutation in acute megakaryoblastic leukaemia. Leukemia 2009;23(5):852-5
  5. Vannucchi AM, et al. Mutations and prognosis in primary myelofibrosis. Leukemia 2013;27(9):1861-9
  6. Rumi E, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 2014;123(10):1544-51
  7. Arber DA, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127(20):2391-405
Last updated: 2018-11-12 20:40:42 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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