CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable.
The single transmembrane domain (TMD) of the human thrombopoietin receptor (TpoR/MPL), encoded by exon 10 of the MPL gene, is a hotspot for somatic mutations associated with myeloproliferative neoplasms (MPNs).
With the discovery in the last 3 years of novel Janus kinase 2 (JAK2) and thrombopoietin receptor (MPL) mutations, the pathogenetic understanding of and clinical practice for myeloproliferative neoplasms (MPNs) have entered a new era.
Genotyping for CALR mutations represents a novel useful tool for establishing a clonal myeloproliferative disorder in JAK2 and MPL wt patients with thrombocytosis and may have prognostic and therapeutic relevance.
A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction.
The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) share similar molecular characteristics in that they frequently harbor hotspot mutations in JAK2, CALR or MPL, leading to activated JAK/STAT signaling.
Myeloproliferative neoplasms (MPNs) are stem cell-derived clonal myeloid malignancies characterized by a unique somatic mutational profile since three mutually exclusive mutations (JAK2V617F, MPL, and CALR) sustain the great majority of the cases.
To investigate its mutation types and prevalence in Chinese patients with myeloproliferative neoplasms (MPN), we performed mutation detection on MPL exon10 in 103 JAK2V617F-negative MPN patients by single strand conformation polymorphism (SSCP) and allele-specific PCR (AS-PCR) combined with sequencing.
Important changes include (1) the change of nomenclature of myeloproliferative disorder to myeloproliferative neoplasm emphasizing the clonal nature of these disorders; (2) the classification of mast cell disease as an MPN; (3) the reorganization of the eosinophilic disorders into a molecularly defined category of PDGFRA, PDGFRB and FGFR1-associated myeloid and lymphoid neoplasms with eosinophilia and chronic eosinophilic leukemia, not otherwise specified; and (4) refinement of the diagnostic criteria for PV, ET and PMF incorporating recently described molecular markers, JAK2V617F, JAK2 exon 12 mutations and MPL mutations.
Somatic calreticulin (CALR), Janus kinase 2 (JAK2), and thrombopoietin receptor (MPL) mutations essentially show mutual exclusion in myeloproliferative neoplasms (MPN), suggesting that they activate common oncogenic pathways.
The majority of patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN) harbor mutations in JAK2 or MPL, which lead to constitutive activation of the JAK/STAT, PI3K and ERK signaling pathways.
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).
Laboratory practice guidelines for detecting and reporting JAK2 and MPL mutations in myeloproliferative neoplasms: a report of the Association for Molecular Pathology.
More recently, activating mutations in the thrombopoietin receptor and in JAK2 exon 12 have been identified in JAK2V617F negative myeloproliferative disorders.
The classic myeloproliferative neoplasms (MPNs) include polycythemia vera and essential thrombocythemia; their molecular basis has been described only recently with the demonstration of recurrent mutations in JAK2 or MPL.
The 2008 WHO criteria for the diagnosis and classification of myeloproliferative neoplasms (MPN) rely in part upon the assessment of mutations in JAK2 and MPL genes.
The myeloproliferative leukemia virus oncogene, MPL, a homodimeric receptor activated by thrombopoietin (THPO), is mutated in myeloproliferative disorders but rarely in AML.
The discovery of activating mutations in JAK2 and MPL in a majority of patients with myeloproliferative neoplasms (MPN) has led to the rapid clinical development of several JAK kinase inhibitors.