Deposition of transforming growth factor-β in the marrow in myelofibrosis, and the intracellular localization and secretion of TGF-β by leukemic cells

• Published in: American journal of clinical pathology Vol. 103; no. 5; pp. 574 - 582
• Main Authors: JOHNSTON, J. B, DALAL, B. I, ISRAELS, S. J, OH, S, MCMILLAN, E, BEGLEITER, A, MICHAUD, G, ISRAELS, L. G, GREENBERG, A. H
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Society of Clinical Pathologists 01.05.1995
• Subjects: Adult; Aged; Biological and medical sciences; Blotting, Northern; Bone Marrow - metabolism; Female; Hematology; Humans; Investigative techniques, diagnostic techniques (general aspects); Leukemia - metabolism; Male; Medical sciences; Middle Aged; Monocytes - metabolism; Neutrophils - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Primary Myelofibrosis - metabolism; RNA, Messenger - analysis; T-Lymphocytes - metabolism; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Human; Immunohistochemistry; Myelofibrosis; Transforming growth factor β; Transforming growth factor; Leukemia; Cytokine; Malignant hemopathy; Hemopathy; Large granular lymphocyte; Case study; Pathology; Myeloproliferative syndrome; Polypeptide; Lymphoproliferative syndrome; Bone marrow; Growth factor
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/ajcp/103.5.574

The marrows of 10 patients with hematologic malignancies were examined by immunohistochemistry using anti TGF-beta antibody, CC(1-30), which detects secreted TGF-beta, and compared with four normal marrows. TGF-beta was not demonstrated in marrows with a normal level of reticulin fibrosis; however, TGF-beta was observed within collagen in marrows having collagen fibrosis or increased reticulin fibrosis. The extent of TGF-beta deposition paralleled the severity of fibrosis (P < .0001), and occurred even with normal or reduced numbers of megakaryocytes. Using another TGF-beta antibody, LC(1-30), which detects intracellular TGF-beta, TGF-beta was detected by immunofluorescence in discrete sites in the cytoplasm of immature and mature myeloid and large granular lymphocytic leukemia cells. These sites colocalized with areas detected by an anti-granule antibody (D545) suggesting that TGF-beta was stored in granules. However, neither the TGF-beta mRNA content nor the degree of TGF-beta secretion by these leukemic cells correlated with the extent of TGF-beta deposition in the marrow. Thus, TGF-beta deposition in marrow may contribute to myelofibrosis, but the source of this cytokine in the absence of megakaryocytes requires further study.