Shared and Tissue-Specific Expression Signatures between Bone Marrow from Primary Myelofibrosis and Essential Thrombocythemia

Shared and Distinctive Ultrastructural Abnormalities Expressed by Megakaryocytes in Bone Marrow and Spleen From Patients With Myelofibrosis

“…Therefore, in addition to transcription factors, this process is limited by lipid bioavailability. Consistent with our previous reported that impaired cholesterol homeostasis is the top eight hit of the expression signature of MF BM ( 33 ), our TEM observations indicate that the membranes of megakaryocytes from MF BM present abnormalities (thick plasma membrane and nuclear membrane with large pores) usually associated with poor lipid content. In addition, these cells present in their cytoplasm numerous glycosomes, suggesting that their glycogen metabolism is skewed toward accumulation of acid-insoluble polyglucosan.…”

“…Genes involved in glycogen metabolism ( 32 ) and mitochondrial function were identified by computer searching using the websites and . The levels of their expression in microarrays of bone marrow (BM) from myelofibrosis patients vs healthy controls (HC) are from ( 33 ) and the original data are deposited in the Gene Expression Omnibus database, .…”

“…Genes involved in glycogen metabolism (32) and mitochondrial function were identified by computer searching using the websites https://www.genecards.org/ and https://www.kegg.jp/. The levels of their expression in microarrays of bone marrow (BM) from myelofibrosis patients vs healthy controls (HC) are from (33) Semi-thin sections of both BM and spleen from MF patients contain numbers of megakaryocytes 1.5-fold greater than those detected in BM from HC while megakaryocytes are barely detectable in normal spleen ( Figures 1A-C). As previously described (20, 22), megakaryocytes in BM are small and organized in clusters ( Figure 1A).…”

Novel targets to cure primary myelofibrosis from studies on Gata1low mice

“…The comparison of the expression signature of bone marrow from Gata1 low mice and PMF patients identified common abnormalities in 12 genes of the noncanonical TGF-β signaling 67,70 which include Jun, JUNB, FOS, FOSB, HIPK2, ID1, GADD45b, BMP4, BMP7, EVI1, STAT1, and IL8. 50,71 Jun, JUNB, FOS, and FOSB are transcription factors involved in the formation of the complex AP-1 (activator protein 1), which regulate gene expression in myelomonocytic cells and recently suggested by the Weissman laboratory of be responsible to induce fibrosis in multiple organs, including in bone marrow. 72 Altered expression of HIPK2 (homeodomain-interacting protein kinase 2) has been implicated in the development of kidney fibrosis.…”

“…The identification of biomarkers to evaluate disease progression or response to therapy is another important facet in the process to address the clinical need of a disease. The comparison of the expression signature of bone marrow from Gata1 low mice and PMF patients identified common abnormalities in 12 genes of the noncanonical TGF‐β signaling which include Jun, JUNB, FOS, FOSB, HIPK2, ID1, GADD45b, BMP4, BMP7, EVI1, STAT1, and IL8 . Jun, JUNB, FOS, and FOSB are transcription factors involved in the formation of the complex AP‐1 (activator protein 1), which regulate gene expression in myelomonocytic cells and recently suggested by the Weissman laboratory of be responsible to induce fibrosis in multiple organs, including in bone marrow .…”