Correlation of the Number of TGFβF1-Expressing Atypical Megakaryocytes with the Degree of Bone Marrow Stroma Fibrosis and Osteosclerosis in Patients with Essential Thrombocythemia and Different Stages of Primary Myelofibrosis

DI Chebotarev, AM Kovrigina, AL Melikyan

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Dmitrii Ilich Chebotarev, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(916)091-27-09; e-mail:

For citation: Chebotarev DI, Kovrigina AM, Melikyan AL. Correlation of the Number of TGFβF1-Expressing Atypical Megakaryocytes with the Degree of Bone Marrow Stroma Fibrosis and Osteosclerosis in Patients with Essential Thrombocythemia and Different Stages of Primary Myelofibrosis. Clinical oncohematology. 2022;15(1):76–84. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-76-84


Background. As morphological pattern of bone marrow (BM) biopsy samples at advanced stages of clonal evolution in essential thrombocythemia (ET) appears similar to that in the development of post-thrombocythemic myelofibrosis and primary myelofibrosis (PMF), the expression of fibrogenesis factors by atypical megakaryocytes (MKC) acquires increased interest.

Aim. To study the expression of the transforming growth factor TGFβF1 by atypical MKC; to relate the number of TGFβF1-positive MKCs with the degree of BM stroma fibrosis and trabecular bone changes in patients with ET and different PMF stages.

Materials & Methods. BM biopsy samples of ET and PMF patients, obtained before cytoreductive therapy, were subjected to histochemical study with Gomori stain and Masson trichrome as well as to CD42b and TGFβF1 antibody immunohistochemical assays. The degree of myelofibrosis and osteosclerosis was estimated by semi-quantitative method in accordance with the European Consensus guidelines. The morphological characteristics of atypical MKC included the comparative evaluation of nuclear-cytoplasmic ratio.

Results. The number of MKCs with high nuclear-cytoplasmic ratio was significantly higher in BM biopsy samples of patients with pre-fibrosis/early PMF (pre-PMF) stage and fibrosis stage of PMF (f-PMF) compared with BM biopsy samples of ET patients. The analysis of TGFβF1 expression showed different numbers of positive MKCs in the study groups. The matching of the number of TGFβF1-positive MKCs with the degree of myelofibrosis and osteosclerosis, with no regard to nosologic entities, revealed significant moderate correlation between these features (r = 0.431, = 0.001 и r = 0.499, = 0.001, respectively). In 55 % of pre-PMF patients’ BM biopsy samples, histochemical study with Masson trichrome stain visualized minimal immature osteoid deposits on bone trabeculae. Similar changes were also identified in f-PMF patients’ BM biopsy samples, whereas the ET patients’ samples featured none of them.

Conclusion. The results of the study prove that the pathological clone of MKC with TGFβF1 expression affects myelofibrosis and osteosclerosis processes whose manifestation in BM biopsy samples is associated with the number of TGFβF1-expressing atypical MKCs.

Keywords: primary myelofibrosis, pre-fibrosis and fibrosis stages, essential thrombocythemia, osteosclerosis, TGFβF1, pathomorphology, immunohistochemistry.

Received: August 12, 2021

Accepted: November 30, 2021

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