Combined MEK and JAK inhibition abrogates murine myeloproliferative neoplasm
نویسندگان
چکیده
منابع مشابه
Combined MEK and JAK inhibition abrogates murine myeloproliferative neoplasm.
Overactive RAS signaling is prevalent in juvenile myelomonocytic leukemia (JMML) and the myeloproliferative variant of chronic myelomonocytic leukemia (MP-CMML) in humans, and both are refractory to conventional chemotherapy. Conditional activation of a constitutively active oncogenic Nras (NrasG12D/G12D) in murine hematopoietic cells promotes an acute myeloproliferative neoplasm (MPN) that rec...
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Children with neurofibromatosis type 1 (NF1) are predisposed to juvenile myelomonocytic leukemia (JMML), an aggressive myeloproliferative neoplasm (MPN) that is refractory to conventional chemotherapy. Conditional inactivation of the Nf1 tumor suppressor in hematopoietic cells of mice causes a progressive MPN that accurately models JMML and chronic myelomonocytic leukemia (CMML). We characteriz...
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Ruxolitinib is a small-molecule inhibitor of the JAK kinases, which has been approved for the treatment of myelofibrosis, a rare myeloproliferative neoplasm (MPN), but clinical trials are also being conducted in inflammatory-driven solid tumors. Increased infection rates have been reported in ruxolitinib-treated patients, and natural killer (NK) cells are immune effector cells known to eliminat...
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27 Introduction The Janus kinases (JAKs) are a family of 4 nonreceptor tyrosine kinases that play an essential role in mediating cytokine signalling. JAKs associate with cytokine receptors that lack intrinsic kinase activity to mediate cytokine-induced signal transduction via the activation of the STAT transcription factors and other signalling pathways (Figure 1, page 28).1,2 The 4 family memb...
متن کاملIntegrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis.
Genomic studies have identified somatic alterations in the majority of myeloproliferative neoplasms (MPN) patients, including JAK2 mutations in the majority of MPN patients and CALR mutations in JAK2-negative MPN patients. However, the role of JAK-STAT pathway activation in different MPNs, and in patients without JAK2 mutations, has not been definitively delineated. We used expression profiling...
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ژورنال
عنوان ژورنال: Journal of Clinical Investigation
سال: 2014
ISSN: 0021-9738
DOI: 10.1172/jci74182