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Ruxolitinib/nilotinib cotreatment inhibits leukemia-propagating cells in Philadelphia chromosome-positive ALL

Overview of attention for article published in Journal of Translational Medicine, August 2017
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Title
Ruxolitinib/nilotinib cotreatment inhibits leukemia-propagating cells in Philadelphia chromosome-positive ALL
Published in
Journal of Translational Medicine, August 2017
DOI 10.1186/s12967-017-1286-5
Pubmed ID
Authors

Yuan Kong, Yi-Lin Wu, Yang Song, Min-Min Shi, Xie-Na Cao, Hong-Yan Zhao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Jun Huang

Abstract

As one of the major treatment obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL), relapse of Ph(+)ALL may result from the persistence of leukemia-propagating cells (LPCs). Research using a xenograft mouse assay recently determined that LPCs were enriched in the CD34(+)CD38(-)CD58(-) fraction in human Ph(+)ALL. Additionally, a cohort study demonstrated that Ph(+)ALL patients with a LPCs phenotype at diagnosis exhibited a significantly higher cumulative incidence of relapse than those with the other cell phenotypes even with uniform front-line imatinib-based therapy pre- and post-allotransplant, thus highlighting the need for novel LPCs-based therapeutic strategies. RNA sequencing (RNA-Seq) and real-time quantitative polymerase chain reaction (qRT-PCR) were performed to analyze the gene expression profiles of the sorted LPCs and other cell fractions from patients with de novo Ph(+)ALL. In order to assess the effects of the selective BCR-ABL and/or Janus kinase (JAK)2 inhibition therapy by the treatment with single agents or a combination of ruxolitinib and imatinib or nilotinib on Ph(+)ALL LPCs, drug-induced apoptosis of LPCs was investigated in vitro, as well as in vivo using sublethally irradiated and anti-CD122-conditioned NOD/SCID xenograft mouse assay. Moreover, western blot analyses were performed on the bone marrow cells harvested from the different groups of recipient mice. RNA-Seq and qRT-PCR demonstrated that JAK2 was more highly expressed in the sorted LPCs than in the other cell fractions in de novo Ph(+)ALL patients. Combination treatment with a selective JAK1/JAK2 inhibitor (ruxolitinib) and nilotinib more effectively eliminated LPCs than either therapy alone or both in vitro and in humanized Ph(+)ALL mice by reducing phospho-CrKL and phospho-JAK2 activities at the molecular level. In summary, this pre-clinical study provides a scientific rationale for simultaneously targeting BCR-ABL and JAK2 activities as a promising anti-LPCs therapeutic approach for patients with de novo Ph(+)ALL.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 6 22%
Researcher 4 15%
Student > Ph. D. Student 4 15%
Student > Bachelor 3 11%
Student > Doctoral Student 3 11%
Other 2 7%
Unknown 5 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 22%
Medicine and Dentistry 5 19%
Agricultural and Biological Sciences 2 7%
Psychology 2 7%
Immunology and Microbiology 1 4%
Other 2 7%
Unknown 9 33%

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 12 September 2017.
All research outputs
#8,967,722
of 14,298,996 outputs
Outputs from Journal of Translational Medicine
#1,540
of 2,758 outputs
Outputs of similar age
#156,776
of 269,214 outputs
Outputs of similar age from Journal of Translational Medicine
#2
of 2 outputs
Altmetric has tracked 14,298,996 research outputs across all sources so far. This one is in the 24th percentile – i.e., 24% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,758 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 269,214 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 2 others from the same source and published within six weeks on either side of this one.