Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples. Significant overexpression of TGF-β1 was also observed in murine clonal MPL(W515L) megakaryocytic cells. TGF-β1 stimulated the deposition of excessive collagen by mesenchymal stromal cells (MSCs) by activating the TGF-β receptor I kinase (ALK5)/Smad3 pathway. MSCs derived from MPL(W515L) mice demonstrated sustained overproduction of both collagen I and collagen III, effects that were abrogated by ALK5 inhibition in vitro and in vivo. Importantly, use of galunisertib, a clinically active ALK5 inhibitor, significantly improved MF in both MPL(W515L) and JAK2(V617F) mouse models. These data demonstrate the role of malignant hematopoietic stem cell (HSC)/TGF-β/MSC axis in the pathogenesis of MF, and provide a preclinical rationale for ALK5 blockade as a therapeutic strategy in MF.
Pharmacology, Toxicology and Pharmaceutical Science
2
5%
Chemistry
1
2%
Other
1
2%
Unknown
14
34%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 8. 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 28 August 2025.
All research outputs
#6,591,416
of 34,234,015 outputs
Outputs from JCI Insight
#2,102
of 5,113 outputs
Outputs of similar age
#83,196
of 354,496 outputs
Outputs of similar age from JCI Insight
#61
of 127 outputs
Altmetric has tracked 34,234,015 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,113 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.6. This one has gotten more attention than average, scoring higher than 58% of its peers.
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 354,496 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 76% of its contemporaries.
We're also able to compare this research output to 127 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
