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PDGFRb regulation in murine myelofibrosis
fibrotic bone marrow and remained increased in overt fibrotic bone marrow of 15-month-old Gata-1low mice.
Differential expression of receptor tyrosine kinases and their ligands in myelofibrosis
Since receptor tyrosine kinases (RTK) and RTK-activat- ing ligands have been attributed an important role in myelofibrosis, we investigated transcriptomic changes by RNA sequencing (RNAseq) analyses with a focus on RTK
(Figure 2A) and their cognate ligands (Figure 2B). Interestingly, a high number of RTK showed a significant increase in gene expression; among which Ptk7, Tie1, Flt1, Fgfr1 and the PDGF receptors Pdgfra and Pdgfrb. Although many ligands were not significantly regulated in early fibrotic bone marrow of Gata-1low mice, we observed an induction of Ptn, Efnb1, Pgf, Angpt2, Angpt4, Igf2 and Efna2. To classify transcriptionally up-regulated genes to their biological function, we further performed gene ontology
I
ABCD
EFGH
Figure 1. Characteristics of the Gata-1low mouse model for primary myelofibrosis at 5 months (5 M), 10 months (10 M), and 15 months (15 M) of age. (A) Body weight of Gata-1low mice and age-matched wild-type (WT) controls. (B) Spleen weight per g body weight. (C) Liver weight per g body weight. (D) Red blood cell (RBC) counts. (E) White blood cell (WBC) counts. (F) Platelet (PLT) counts. (G) Quantitative polymerase chain reaction analyses of type I collagen Col1a1 and (H) type III col- lagen Col3a1. (I) Representative images of reticulum-stained femoral bone marrow showing increasing amount of reticulum fibers in the bone marrow of Gata-1low mice, indicated by red arrowheads. Scale bar=50 mm. n=7-11 mice per group. *P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001 versus the control group by Student t-test.
haematologica | 2020; 105(8)
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