AURKA contributes to Janus-kinase-2 (JAK2) activation and increased AURKA protein levels were reported in CD34+ and CD41+ cells of myeloproliferative neoplasm patients, leading to aneuploidy and aberrant megakaryopoiesis.
While JAK2 inhibitor therapy provides substantial clinical benefit in MPN patients, the identification of alternative therapeutic targets is needed to reverse MPN pathogenesis and control malignant hematopoiesis.
Later studies identified that PMF, as the others MPNs, is associated with mutations activating the thrombopoietin/JAK2 axis raising great hope that JAK inhibitors may be effective to treat the disease.
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.
Calreticulin (CALR) gene mutations are currently recommended as biomarkers in diagnosis of patients with myeloproliferative neoplasms (MPN) with Jak2V617F negative phenotype.
In the absence of BCR-ABL, the conventional diagnostic algorithm recommends JAK2V617F mutation testing to support diagnosis of other MPN diseases such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
This demonstrates that compensatory ERK activation limits the efficacy of JAK2 inhibition and dual JAK/MEK inhibition provides an opportunity for improved therapeutic efficacy in MPNs and in other malignancies driven by aberrant JAK-STAT signaling.
Myeloproliferative neoplasms (MPNs) driver mutations are usually found in JAK2, MPL, and CALR genes; however, 10%-15% of cases are triple negative (TN).
The V617F mutation in the JH2 domain of JAK2 is an oncogenic driver in several myeloproliferative neoplasms (MPNs), including essential thrombocythemia, myelofibrosis, and polycythemia vera (PV).
This review focusses on the role of JAK2 and the JAK/STAT pathway in MPN and LPN, whether there is a role for the genetic background in the occurrence of both MPN and LPN, and whether there is a role for cytoreductive drugs in the occurrence of both MPN and LPN.
The major weakness of most knock-in JAK2V617F mouse models is the presence of the JAK2 mutation in all rather than in a few hematopoietic stem cells (HSC), like in human "early stage" myeloproliferative neoplasms (MPN).
The link between MA and JAK2 mutant allele burden implies that allele burden has a role not only in clinical phenotype and disease evolution in MPN patients, but also in the overall methylation landscape of the mutated cells.
Unique Case of Myeloproliferative Neoplasm with Two Rare Clonal Abnormalities: Rare JAK2 Exon 12 Mutation and Rare e14a3 (b3a3) BCR/ABL Fusion Transcript.
Primary Myelofibrosis (PMF) is a myeloproliferative disorder associated with JAK2V617F, Calreticulin (CALR) indels, and MPLW515L/K mutations activating the tyrosine kinase JAK2 and its downstream signaling pathway.
While TERT rs2736100_C tended to have a more general, non-specific effect on all MPNs, the JAK2 46/1 haplotype was essentially predisposed to the JAK2V617F-positive MPNs.
The identification of JAK2 mutations as disease-initiating in myeloproliferative neoplasms (MPNs) has led to new and effective therapies for these diseases.
The occurrence in most patients affected by myeloproliferative neoplasms (MPNs) of driver mutations resulting in the constitutive activation of JAK2-dependent signaling identified the deregulated JAK-STAT signal transduction pathway as the major pathogenic mechanism of MPNs.
The objective of this review is to characterize studies on BCR-ABL1-negative chronic myeloproliferative neoplasms and to compare the frequency of JAK2, MPL and CALR mutations in PV, ET and PMF.