MPL Exon 10 Mutation Detection, Bone Marrow
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
DNA sequence mutations in exon 10 of the myeloproliferative leukemia virus oncogene (MPL) have been detected in approximately 5% of patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET), which are hematopoietic neoplasms classified within the broad category of myeloproliferative neoplasms. MPL codes for a transmembrane tyrosine kinase and the most common MPL mutations are single base pair substitutions at codon 515. These mutations have been shown to promote constitutive, cytokine-independent activation of the JAK/STAT signaling pathway and contribute to the oncogenic phenotype. At least 8 different MPL exon 10 mutations have been identified in PMF and ET to date, and mutations outside of exon 10 have not yet been reported. The vast majority of MPL mutations have been found in specimens testing negative for the most common mutation identified in myeloproliferative neoplasms, JAK2 V716F, although a small number of cases with both types of mutations have been reported. MPL mutations have not been identified in patients with polycythemia vera, chronic myelogenous leukemia, or other myeloid neoplasms.
Identification of MPL mutations can aid in the diagnosis of a myeloproliferative neoplasm and is highly suggestive of either PMF or ET.
Aiding in the distinction between a reactive cytosis and a myeloproliferative neoplasm in bone marrow specimens
The results will be reported as 1 of 2 states:
-Negative for MPL exon 10 mutation
-Positive for MPL exon 10 mutation
If the result is positive, a description of the mutation at the nucleotide level and the altered protein sequence is reported.
Positive mutation status is highly suggestive of a myeloproliferative neoplasm, but must be correlated with clinical and other laboratory features for a definitive diagnosis. Negative mutation status does not exclude the presence of a myeloproliferative or other neoplasm.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A positive result is not specific for a particular diagnosis and clinicopathologic correlation is necessary in all cases.
A negative result does not exclude the presence of a myeloproliferative or other neoplasm.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Pikman Y, Lee BH, Mercher T, et al: MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. FLoS Med 2006;3:e270
2. Pardanani A, Levine R, Lasho T, et al: MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006;15:3472
3. Kilpivaara O, Levine RL: JAK2 and MPL mutations in myeloproliferative neoplasms: discovery and science. Leukemia 2008;22:1813-1817