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).
Studies have shown that mutant calreticulin (CALR) constitutively activates the thrombopoietin (TPO) receptor MPL and thus plays a causal role in the development of myeloproliferative neoplasms (MPNs).
In summary, the abnormal SOCE regulation of Ca2+ flows in megakaryocytes contributes to the pathophysiology of CALR-mutated myeloproliferative neoplasms.
Histone deacetylase 6 (HDAC6) controls JAK2 translation and protein stability, and has been implicated in JAK2-driven diseases best exemplified by Myeloproliferative Neoplasms (MPNs).
Studies have shown that mutant calreticulin (CALR) constitutively activates the thrombopoietin (TPO) receptor MPL and thus plays a causal role in the development of myeloproliferative neoplasms (MPNs).
Sequential mutational evaluation of CALR -mutated myeloproliferative neoplasms with thrombocytosis reveals an association between CALR allele burden evolution and disease progression.
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.
Developing Janus kinase 2 (JAK2) inhibitors has become a significant focus for small-molecule drug discovery programs in recent years because the inhibition of JAK2 may be an effective approach for the treatment of myeloproliferative neoplasm.
Identification of janus kinase 2 (JAK2) mutation even in absence of myeloproliferative disorders (MPNs) was found to be related to venous thromboembolism occurrence.
Primary and post-ET/PV myelofibrosis are myeloproliferative neoplasms harboring in most cases driving mutations in JAK2, CALR or MPL, and a variable number of additional mutations in other genes.
The most prominent genes of this locus are programmed death ligands 1 and 2 (PDL1/PDL2), with the amplification of PDL1 being a hallmark of both classical Hodgkin and primary mediastinal B cell lymphoma, and Janus kinase 2 (JAK2), which is point-mutated in myeloproliferative neoplasms and other myeloid malignancies, and rearranged in PCM1-JAK2-positive myeloid/lymphoid neoplasms with eosinophila.
BCR-ABL1-negative myeloproliferative disorders and chronic myeloid leukaemia are haematologic malignancies characterised by single and mutually exclusive genetic alterations.
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.
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.
JAK2 variants were detected at a higher frequency in the MPN>AML cohort (15.3%) in comparison with the MPN (4.6%; P < .001) and AML cohorts (5.2%; P < .001).
The identification of JAK2 mutations as disease-initiating in myeloproliferative neoplasms (MPNs) has led to new and effective therapies for these diseases.
Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the constitutive tyrosine kinase (TK) activity of the BCR-ABL1 fusion protein.