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Tyrosine 625 plays a key role and cooperates with tyrosine 630 in MPL W515L-induced signaling and myeloproliferative neoplasms

Overview of attention for article published in Cell & Bioscience, May 2016
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Title
Tyrosine 625 plays a key role and cooperates with tyrosine 630 in MPL W515L-induced signaling and myeloproliferative neoplasms
Published in
Cell & Bioscience, May 2016
DOI 10.1186/s13578-016-0097-3
Pubmed ID
Authors

Chunjie Yu, Qiong Yang, Yuhong Chen, Demin Wang, Ross Levine, John Crispino, Qiang Wen, Zan Huang

Abstract

Myeloproliferative neoplasms (MPN) are a group of blood cancers that boost normal blood cell production in the bone marrow. Abnormal mutations in stem cells were found accompanying with the occurrence of MPN. It has been shown that MPL mutations (MPL W515L or MPL W515K) were involved in patients with MPN. Since tyrosine residues 625 and 630 mediate normal MPL signaling, whether them affect MPL W515L-induced myeloproliferative neoplasms (MPNs) is unknown. In this study, we further tested their functions in MPL W515L-induced myeloproliferative neoplasms (MPNs) by substituting either or both of them with phenylalanine in MPL W515L (termed as MPL515/625, MPL515/630 and MPL515/625/630, respectively). In vitro, MPL515/630 but not MPL515/625 or MPL515/625/630 retained the ability to induce TPO-independent proliferation and increase colony-forming unit megakaryocytes (CFU-Mk). Accordingly, differential activation of the downstream signaling by four mutants was observed and constitutively active STAT5 or AKT instead of STAT3 partially compensated MPL515/625/630 function. Further support this, STAT5-deficiency impaired MPL W515L-induced CFU-Mk expansion. In vivo, MPL515/630 but not MPL515/625 or MPL515/625/630 induced typical features of MPNs with high WBC and platelet counts, splenomegaly, hepatomegaly and hypercellularity in the bone marrow. Surprisingly, MPL515/625 also caused hypercellularity of bone marrow and splenomegaly without any other significant features. We also observed differential effects of the four mutants on progenitors, myeloid cells and megakaryocytes. Our studies have revealed distinct features of tyrosine sites 625 and 630 in mediating MPL W515L-induced megakaryocyte hyperproliferation and MPNs. Our study also suggests that MPL cytosolic phosphorylated Y625 and flanking amino acids could become targets for pharmacologic inhibition in MPNs.

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Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 2 40%
Student > Bachelor 1 20%
Unknown 2 40%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 40%
Computer Science 1 20%
Unknown 2 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 May 2016.
All research outputs
#17,806,995
of 22,875,477 outputs
Outputs from Cell & Bioscience
#475
of 935 outputs
Outputs of similar age
#235,758
of 333,421 outputs
Outputs of similar age from Cell & Bioscience
#6
of 18 outputs
Altmetric has tracked 22,875,477 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 935 research outputs from this source. They receive a mean Attention Score of 3.7. This one is in the 39th percentile – i.e., 39% of its peers scored the same or lower than it.
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We're also able to compare this research output to 18 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.