Fibrosis of the Bone Marrow: Content and Causes

McCarthy, Donald

doi:10.1111/j.1365-2141.1985.tb02956.x

Cited by 173 publications

(60 citation statements)

References 42 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Especially, PDGF and platelet factor 4 (PF4) which are located in a-granules of megakaryocytes, are hypothesized to be responsible for the pathogenesis of idiopathic myelofibrosis (Bernabei et al, 1986;Castro-Malaspina, 1984;McCarthy, 1985). PDGF is an effective mitogen for fibroblasts (Heldin, 1992;Ross et al, 1986) whereas PF4 inhibits collagenase activity (Hiti-Harper, 1978).…”

Section: Discussionmentioning

confidence: 99%

“…The purpose of the present study was to clarify the causes of PEG-rHuMGDFand TPO-induced myelofibrosis. The previous findings regarding idiopathic myelofibrosis in humans may provide a clue to the causes of PEG-rHuMGDF-and TPO-induced myelofibrosis as marrow megakaryocytes are also markedly increased in idiopathic myelofibrosis (Castro-Malaspina, 1984;McCarthy, 1985). Conversely, PEG-rHuMGDF-and TPO-induced myelofibrosis in animals may be a good model for the investigation of the pathogenesis of idiopathic myelofibrosis.…”

mentioning

confidence: 99%

“…Several investigators have hypothesized that growth factors derived from megakaryocytes such as TGF-b and plateletderived growth factor (PDGF) are responsible for the pathogenesis of idiopathic myelofibrosis (Bernabei et al, 1986;Castro-Malaspina, 1984;McCarthy, 1985;Wickenhauser et al, 1995;Yan et al, 1996). TGF-b is a pleiotropic multifunctional cytokine (the most abundant isoform of TGF-b is TGF-b1), and strongly stimulates the biosynthesis of type I and type III collagen, fibronectin and proteoglycans from fibroblasts (Kimura et al, 1989;Roberts et al, 1986).…”

mentioning

confidence: 99%

See 2 more Smart Citations

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

et al. 1997

View full text Add to dashboard Cite

Summary. Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 mg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6-8 d followed by gradual decreases to control levels at 10-20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6-8 d, the levels of transforming growth factor-b1 (TGF-b1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7-and 2-fold, respectively. The elevated levels of TGF-b1 were gradually reduced to baseline levels at 13-20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 mg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-b1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

et al. 1997

View full text Add to dashboard Cite

show abstract

“…1 Idiopathic Myelofibrosis (IMF) is an infrequent chronic myeloproliferative disorder characterized by varying degrees of bone marrow fibrosis and extra medullary hematopoiesis, with the fibrosis being a reactive phenomenon to a neoplastic proliferation of a pluripotent hematopoietic stem cell. IMF is heterogeneous in presentation and clinical course, with anemia being one of the most important problems.…”

Section: Introductionmentioning

confidence: 99%

Idiopathic myelofibrosis mimicking hemolytic anemia

Baral

Aryal

2012

J Pathol Nep

View full text Add to dashboard Cite

Idiopathic Myelofibrosis is an infrequent chronic myeloproliferative disorder characterized by varying degrees of bone marrow fibrosis and extra medullary hematopoiesis, with the fibrosis being a reactive phenomenon to a neoplastic proliferation of a pluripotent hematopoietic stem cell. Idiopathic Myelofibrosis is heterogeneous in presentation and clinical course, with anemia being one of the most important problems. We present a case of a 59 year old male who presented with severe anemia, the peripheral blood picture mimicking hemolysis with numerous schistocytes and teardrop cells.Journal of Pathology of Nepal (2012) Vol. 2, 323-327DOI: http://dx.doi.org/10.3126/jpn.v2i4.6888

show abstract

“…The histologic features of marrow fibrosis include excessive deposits of extracellular matrix proteins, particularly reticulin, along with hypercellularity, neoangiogenesis, and fibroblast over proliferation [1]. Marrow fibrosis occurs in the setting of a variety of primary hematologic neoplastic processes; these include, most prominently, (a) primary idiopathic myelofibrosis associated with myeloid metaplasia, (b) the late, or ''spent'' phase of polycythemia vera, (c) a subset of patients with chronic myelogenous leukemia, and (d) some cases of acute megakaryocytic leukemia [2].…”

Section: Introductionmentioning

confidence: 99%

Peripheral monocytes and CD4⁺ cells are potential Sources for increased circulating levels of TGF‐β and substance P in autoimmune myelofibrosis

Harrison¹,

Corcoran²,

Joshi³

et al. 2005

American J Hematol

View full text Add to dashboard Cite

Myelofibrosis is an uncommon phenomenon associated with a variety of neoplastic and inflammatory processes. Although there is evidence that cytokines elaborated by clonal malignant hematopoietic cells are implicated in myelofibrosis in primary hematologic disorders, there has been little data to date on the pathophysiology of myelofibrosis in autoimmune disorders. Here we report a case of autoimmune myelofibrosis with pancytopenia. Peripheral blood monocytes and CD4-positive lymphocytes produced significantly elevated levels of transforming growth factor b (TGF-b) compared to similar cells from healthy volunteer controls. TGF-b has been implicated in the pathogenesis of myelofibrosis associated with primary hematological malignancies. Furthermore, substance P, previously linked to myelofibrosis, was also detected in elevated levels in the patient's serum and correlated negatively with the levels of the patient's blood counts. These findings suggest a role for both TGF-b and substance P in the pathophysiology of autoimmune myelofibrosis. This is the first report of deregulated production of TGF-b by monocytes in the pathobiology of autoimmune myelofibrosis. Am.

show abstract

Fibrosis of the Bone Marrow: Content and Causes

Cited by 173 publications

References 42 publications

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

Idiopathic myelofibrosis mimicking hemolytic anemia

Peripheral monocytes and CD4⁺ cells are potential Sources for increased circulating levels of TGF‐β and substance P in autoimmune myelofibrosis

Contact Info

Product

Resources

About

Fibrosis of the Bone Marrow: Content and Causes

Cited by 173 publications

References 42 publications

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

Idiopathic myelofibrosis mimicking hemolytic anemia

Peripheral monocytes and CD4+ cells are potential Sources for increased circulating levels of TGF‐β and substance P in autoimmune myelofibrosis

Contact Info

Product

Resources

About

Peripheral monocytes and CD4⁺ cells are potential Sources for increased circulating levels of TGF‐β and substance P in autoimmune myelofibrosis