Myelofibrosis as a dynamic process - correlation between megakaryocyte level, platelet derived growth factor receptor beta (PDGFRb) expression and myelofibrosis grade

Introduction: Megakaryocytes (MKC) produce the Platelet Derived Growth Factor (PDGF) which is a ligand of the Platelet Derived Growth Factor Receptor (PDGFR). PDGFR activation has mitotic effect on fibroblasts. There is a proven correlation between the myelofibrosis (MF) grade and the amount of PDGFRB expressing fibroblasts (PDGFRB score).
Aim: The aim of this study was to investigate the correlation between the bone marrow MKC content and the MF grade indicating the fiber content, the PDGFRB score indicating the number of activated fibroblasts and platelet level indicating MKC function.
Methods: From 70 patients bone marrow biopsies were obtained from the period of 2008-2011. Patients were classified into 4 groups namely: 1) control group, 2) Myeloproliferative Neoplasm (MPN) group, 3) Myelodysplasic Syndrome (MDS) group, 4) Other group. Platelet level and JAK2 mutation status was obtained for MedSolution database. The MF grade and the PDGFRB score were verified from bone marrow biopsies. For the total MKC count CD 41 IHC staining was used, where 5 views of high power magnification were randomly selected for counting.
Results: The MKC count was significantly higher in the MPN group (p=0,0323) and the MDS group (p=0,0181) compared to the control group, while there was no significant difference in the other group. Cases with mild (MF1) or advanced (MF2, MF3) fibrosis did not show higher MKC count compared to the non fibrotic group (MF0). There was no significant correlation between the MKC count and the MF grades (Spearman r=0,1756). Cases with extensive fibroblast activation (PDGFRB score 2 and 3) showed significantly higher MKC count compared to cases without fibroblast activation (PDGFRB score 0). There was significant correlation between the MKC count and the PDGFRB score (Spearman r=0,3353). Comparing the MKC count between JAK positive and JAK negative groups there was no significant difference (p value= 0.6025).
Conclusion: Our results suggest that proliferation of PDGFRB positive fibroblasts precedes the accumulation of reticulin fibers in myelofibrosis. Thus the PDGFR can be a potential therapeutic target of tyrosine kinase inhibitor therapy.