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At least 343 records · Page 19Linked to original sources
PubMed1983

Circulating granulocyte and macrophage progenitor cells in primary and secondary myelofibrosis.

Patients with primary myelofibrosis (PMF) and myelofibrosis secondary to carcinoma (SMF) were compared with regard to circulating granulocyte macrophage progenitor cells (CFU-GM) using in vitro tissue culture techniques. Although increased numbers of CFU-GM had previously been well documented in PMF, few patients with the secondary variety had been studied. Our data indicate that there is an increase in circulating CFU-GM in patients with SMF but it is significantly lower than in those with PMF. It is suggested that in both conditions disruption of the marrow microvascular system results in a release of CFU-GM to the circulation. In PMF stem cell colonization of the spleen with its consequent myeloid metaplasia may be responsible for the additional increase in CFU-GM. The determination of CFU-GM numbers may provide additional data to help to distinguish PMF and SMF in atypical cases where the distinction is unclear.

Adult↗
PubMed1984

The 'spent' phase of polycythaemia vera: hypersplenism in the absence of myelofibrosis.

A clinical phase (spent phase) in the course of polycythaemia vera (PV) cases is described as enlargement of the spleen in spite of treatment, frequent cytopenia of one or several lines, persistent red cell hypervolaemia with considerable increase of plasma volume, persistence of myeloid hyperplasia with no collagen myelofibrosis or osteomyelosclerosis, absence of hepatosplenic erythroblastic metaplasia, as shown by radio-iron kinetics and/or 111In-transferrin scintigraphy. The frequency of this phase was 5% in a study where it was not systematically sought, but it could in fact be greater. Its occurrence is not related to the clinical and biological parameters of PV. On the other hand, it is significantly more frequent and earlier in patients treated by phlebotomies than in those treated by myelosuppression (32P). In four of the 12 cases, this phase was rapidly followed by an acute leukaemia. In eight cases there was a 1-5 year interval before a myelofibrosis with splenic myeloid metaplasia. This evolution could at this stage be delayed by chemotherapy. The efficacy of splenectomy should be studied.

Aged↗
PubMed1984

Platelet factor-4 excretion in myeloproliferative disease: implications for the aetiology of myelofibrosis.

Experimental evidence suggests that the fibroblastic proliferation often associated with the myeloproliferative disorders is not part of the neoplastic process, but is secondary to an unknown stimulus. This stimulus may be a factor derived from platelets which promotes the proliferation of fibroblasts in vitro (PDGF). Platelet-derived growth factor is localized to platelet alpha-granules together with PF4 and beta-TG. As an indicator of alpha-granule release, we have measured PF4 levels in plasma, platelets and urine in 46 normal subjects and 49 patients with myeloproliferative disorders, secondary thrombocytosis and miscellaneous malignancies. All 11 patients with elevated urinary PF4 excretion exhibited myelofibrosis, whereas 11 of 22 patients with documented myelofibrosis had urinary PF4 excretion in the normal range. No correlation was seen between marrow fibrosis and plasma levels or the platelet content of PF4. The data are consistent with the possibility that release of mitogen(s) from platelet or megakaryocyte alpha-granules in some patients with myeloproliferative disorders is pathogenetically related to the development of marrow fibrosis.

Blood Platelets↗
PubMed1985

Characterization of blast cells in chronic granulocytic leukaemia in transformation, acute myelofibrosis and undifferentiated leukaemia. I. Ultrastructural morphology and cytochemistry.

A systematic analysis of the blast cell population was carried out on samples from 50 patients suffering from blast transformation of chronic granulocytic leukaemia (CGL) (31) and of myelofibrosis (4), acute myelofibrosis (AM) (11) and undifferentiated acute leukaemia (4). Transmission electron microscopy (TEM), used in 41 samples, included: morphology and techniques for myeloperoxidase (MPO), platelet-peroxidase (PPO) and acid phosphatase (AP). The majority of cases were also studied by light microscopy cytochemistry and with a battery of cell markers which are reported in the accompanying paper (San Miguel et al, 1985). The characterization of the type(s) of proliferating blasts was made from the integration of ultrastructural and immunological data. TEM morphology allowed the precise recognition of specific granules in basophil and mast-cell precursors and of ferritin particles in blasts of erythroid lineage; these rare cell types were not adequately characterized by other methods. The PPO reaction made possible the identification of pure megakaryoblastic proliferations in 38% of cases, including eight of the 11 with AM; megakaryoblasts were also present in nine of 12 cases with mixed blast cell types. The MPO and AP reactions were useful for the characterization of myeloblasts and monoblasts, respectively. Lymphoblasts could be distinguished from other cell types by TEM morphology and negative MPO and PPO reactions. TEM techniques were valuable for diagnosing correctly the type of blast cell in this study in which only four cases (8%) remained unclassifiable.

Acute Disease↗
PubMed1989

Myelofibrosis in primary myelodysplastic syndromes: a clinico-morphological study of 10 cases.

We describe 10 cases of primary myelodysplastic syndrome in which marrow fibrosis was striking at presentation. All the cases showed trilineage dysplasia with increased megakaryopoiesis and marked reticulin fibrosis. Significant organomegaly was notably absent. This association has hitherto not been highlighted and it is important to distinguish these cases from those of idiopathic myelofibrosis with which they may be confused. Furthermore, their comparatively long survival distinguishes these cases from those previously described as acute myelodysplasia with myelofibrosis and malignant myelosclerosis. The pathogenesis of fibrosis in these cases may be related to disordered megakaryopoiesis and the platelet-derived cytokines that may be released. The treatment of these fibrotic cases remains problematical and further investigation is required.

Adult↗
PubMed1991

Circulating progenitor cells in myelofibrosis: the effect of recombinant alpha 2b interferon in vivo and in vitro.

We have studied circulating progenitor cells in patients with myelofibrosis, the effects of recombinant alpha 2b interferon (IFN) treatment on these cells in vivo and in vitro and the patients' clinical response to IFN treatment. A 75-fold increase in circulating granulocyte macrophage colony forming units (CFU-GM) and a 25-fold increase in multilineage colonies (CFU-GEMM) were seen in the patients compared with controls. Patients who had undergone splenectomy had circulating progenitors within the normal range. IFN treatment of two patients resulted in clinical improvement and reduction in spleen size, but was complicated by a fall in platelet count and persistent malaise. Whilst on treatment the circulating progenitor cells increased up to 5-fold. In contrast, the addition of IFN in vitro to the CFU-GM and CFU-GEMM culture plates resulted in a dose-dependent inhibition of colony growth which was unaffected by the removal of T-cells and monocytes. Thus we confirm that circulating progenitors are raised in patients with myelofibrosis, IFN may be of benefit clinically, reducing spleen size but may increase levels of these cells in vivo. This is in contrast to the inhibitory effect of IFN in vitro on CFU-GM and CFU-GEMM growth.

Colony-Forming Units Assay↗
PubMed1991

Increased intraplatelet levels of platelet-derived growth factor and transforming growth factor-beta in patients with myelofibrosis with myeloid metaplasia.

Platelet-derived growth factor (PDGF) is thought to play some role in the genesis of fibrosis associated with myeloproliferative disorders. In addition, transforming growth factor-beta (TGF-beta) has been confirmed to promote fibrotic process. Both PDGF and TGF-beta have been shown to cooperate with epidermal growth factor (EGF) in regulating the growth of human marrow fibroblasts. All three are contained in platelet alpha-granules. We report the results of a study in patients with myelofibrosis with myeloid metaplasia (MMM). We evaluated PDGF, TGF-beta and EGF-like activities in circulating platelets from patients compared to healthy subjects. In contrast to EGF-like intraplatelet levels which were similar in patients and in normal donors (1-4 ng/10(9) platelets), we found constantly higher values for both PDGF and TGF-beta in MMM patients. In both radioimmunoassay (RIA) and assay for mitogenic activity on human bone marrow fibroblasts, PDGF levels were increased on the average 2-3.5-fold over the levels found in normal donors (P less than 0.01 and P less than 0.001, respectively). PDGF serum levels in patients were consistent with those found in platelets. In platelet-poor plasma (PPP), PDGF concentrations were undetectable or congruent to 2 ng/ml in patients and in control donors as well. The total TGF-beta activity in platelet lysates, determined using a competitive radioreceptor binding assay on Swiss 3T3 mouse cells and an inhibition growth assay on CCL64 cells, was found 2-3-fold increased in patients with MMM as compared to control subjects (P less than 0.003). These results emphasize that, not only PDGF, but also TGF-beta are implicated in the myelofibrosis with myeloid metaplasia.

Adult↗
PubMed1993

Parvovirus B19 induced red cell aplasia in myelofibrosis.

A 38-year-old female presented with moderate anaemia and a leucoerythroblastic blood film. Subsequent investigation showed myelofibrosis in cellular phase. Her haemoglobin quickly and spontaneously recovered with concurrent serological evidence of recent parvovirus B19 infection. This is the first report in the literature of parvovirus causing red cell aplasia in myelofibrosis.

Adult↗
PubMed1993

Characterization of an acute micromegakaryocytic leukaemia: evidence for the pathogenesis of myelofibrosis.

The current hypothesis for the pathogenesis of myelofibrosis involves the intramedullary release of growth factors from defective or abnormal megakaryocytes. We describe a case of an acute micromegakaryocytic leukaemia, in a patient with chronic myelofibrosis, that provides additional evidence for this concept. The micromegakaryocytes, which reached 223 x 10(9)/l, were characterized morphologically by both light and electron microscopy, immunocytochemically and by platelet peroxidase activity. The cells were shown to have a mature cytoplasm, containing alpha granules and the associated proteins; vWF:Ag, fibrinogen, fibronectin and protein S. DNA analysis, by both a Seescan Solitaire Plus image analysis system and flow cytometry, revealed nuclear immaturity, with 92% of cells being diploid. Serum markers of connective tissue synthesis, namely carboxy terminal peptide of procollagen I (PICP), procollagen terminal peptide III (PIIIP) and laminin all increased significantly following transformation and were associated with an increase in platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). These observations support the current hypothesis for bone marrow fibrosis formation and provide, for the first time, a link between in vivo growth factor release, bone marrow stromal turnover and megakaryocyte mass. In addition, the release of biologically active TGF-beta may explain both the increased fibronectin and angiogenesis characteristic of myelofibrotic bone marrow.

Female↗
PubMed1994

Platelet-derived growth factor expression in accelerated and blastic phase of chronic myelogenous leukaemia with myelofibrosis.

Myelofibrosis is sometimes associated with accelerated and blastic phase of chronic myelogenous leukaemia (CML). In order to investigate the role of platelet derived growth factor (PDGF) in this pathogenesis, expression and production of PDGF was studied in the blast cells from 11 patients. Five patients had myelofibrosis with myeloid blasts, while six patients did not show fibrosis, including three with myeloid blasts and three with lymphoid blasts. PDGF-A chain transcript was expressed in most of the patients. On the other hand, PDGF-B chain transcript was detected in all of the five patients with myeloid blasts and with fibrosis, in one of the three patients with myeloid blasts and without fibrosis, and in none of the three lymphoid crisis patients without fibrosis. In the patients with myeloid blasts and with fibrosis, PDGF protein, PDGF-AB and/or PDGF-BB, was found to be secreted from blast cells. In addition, the PDGF activity in the culture of myeloid blasts from two patients with fibrosis was also growth stimulatory for human marrow fibroblasts. These results suggest that expression and secretion of PDGF-AB or PDGF-BB in blast cells play an important role in the pathogenesis of marrow fibrosis associated with accelerated and blastic phase of CML.

Adult↗
PubMed1994

Transforming growth factor-beta and megakaryocytes in the pathogenesis of idiopathic myelofibrosis.

Although the disease is well described, the pathogenesis of bone marrow fibrosis in idiopathic myelofibrosis still remains unclear. We previously reported elevated intraplatelet transforming growth factor-beta (TGF-beta) levels in patients with this myeloproliferative disorder, compared with healthy subjects. Here, in a series of 16 patients, we show that TGF-beta expression is also increased in patients' peripheral blood mononuclear cells (PBMC): (i) at the mRNA level analysed by Northern blot hybridization and/or reverse transcription-polymerase chain reaction (RT-PCR); (ii) and/or at the secreted peptide level as evaluated in conditioned media from patients' mononuclear cells by a growth inhibition assay on CC164 cells. By immunostaining with a polyclonal anti-TGF-beta 1 antibody, TGF-beta was localized in morphologically heterogenous cells; these cells were characterized as megakaryocytes by labelling with a gpIIbIIIa monoclonal antibody. Thus we provide evidence that both TGF-beta and megakaryocytes are linked in the pathogenesis of idiopathic myelofibrosis.

Aged↗
PubMed1988

Hydroxyprolinuria and hypercalcaemia during immobilization in patients with idiopathic myelofibrosis.

Two of three patients with bone pains and hydroxyprolinuria due to idiopathic myelofibrosis developed hypercalcaemia during periods of immobilization. This responded rapidly to cytotoxic therapy with busulphan. Hydroxyproline excretion in the urine was increased compared to ambulant patients with the same disease. These previously unreported findings suggest that immobilization can produce rapid, generalized bone resorption in patients with myelofibrosis.

Adult↗
PubMed1994

Trisomy 14, deletion 20q and t(3;3) (q21;q26) in a case of myelodysplastic syndrome with myelofibrosis.

We describe a patient with trilineage myelodysplasia and hyperplastic megakaryopoiesis associated with significant myelofibrosis at diagnosis, who developed acute myeloid leukaemia two months afterwards. The clinical and pathological features were consistent with a myelodysplasia/myelofibrosis syndrome with leukemic transformation. Cytogenetic investigation showed trisomy 14, del(20q) and t(3;3) (q21;q26). These findings are of possible significance in the understanding of the association between myelodysplasia and myelofibrosis.

Chromosome Deletion↗
PubMed1990

Myelofibrosis discovered after diagnosis of Sweet's syndrome.

Multiple edematous plaques and nodules suddenly developed on the face and neck of a 26-year-old man whose physical examination was said to be normal Because the patient's condition fulfilled the diagnostic criteria of Sweet's syndrome, a further general medical examination and hematologic evaluation were performed. Extensive myelofibrosis was revealed by bone marrow biopsy. This case supports the belief that Sweet's syndrome is a reactive phenomenon. Because myelofibrosis was discovered in this patient after Sweet's syndrome was diagnosed, the importance of having the diagnostic criteria of Sweet's syndrome is emphasized. Careful systemic evaluation is indicated, especially when cutaneous lesions are severe or hematologic values are abnormal.

Adult↗
PubMed1992

Cutaneous myelofibrosis.

Cutaneous extramedullary hematopoiesis is rare, usually occurring in neonates following intrauterine viral infections, hereditary spherocytosis, or the twin transfusion syndrome. Only 20 cases of cutaneous extramedullary hematopoiesis have been reported in adults, all with myelofibrosis. The cutaneous infiltrates may be atypical and difficult to distinguish from leukemia cutis. We have studied a 65-year-old woman with myelofibrosis and approximately 40 violaceous, firm, non-tender cutaneous nodules measuring 1 to 4 cm in diameter, located on her abdomen near a splenectomy scar. Histologically, the lesions had a dense infiltrate of myeloid cells in all stages of maturation, atypical large cells with multilobate nuclei or multiple nuclei, resembling atypical megakaryocytes, and fibroblasts. Although the patient received erythropoietin therapy prior to the development of the nodules, erythroid progenitors were not seen. Reticulin was increased particularly surrounding the atypical megakaryocytes. The myeloid cells stained for chloroacetate esterase and with the polyclonal antibody MAC 387. Atypical megakaryocytes stained for Factor XIIIa and Factor VIII-related antigen. Dendritic Factor XIIIa positive cells were also increased. The skin lesions remain unchanged grossly one year after their development.

Aged↗
PubMed1982

Circulating haematopoietic progenitors in myelofibrosis.

We studied circulating erythroid and granulocyte-monocyte progenitors in 18 patients with idiopathic myelofibrosis and in healthy controls, using the methyl cellulose assay. 9 of the patients had been splenectomized prior to the study. The median number of circulating erythroid burst-forming units (BFU-E) was 8 times higher than that of the controls. 12 patients also had CFU-E (colony-forming unit, erythroid) in the blood. 10 patients had spontaneous BFU-E colony formation, and 8 patients had spontaneous CFU-E colony growth. Granulocyte-monocyte progenitors (CFU-GM) were increased 47 times compared to the controls. There were no differences in colony numbers between splenectomized and non-splenectomized patients. We conclude that in myelofibrosis, circulating erythroid and granulocyte-monocyte progenitors are usually markedly increased in number, but erythroid precursors to a lesser extent than granulocyte-monocyte precursors. Many patients, but not all, show spontaneous erythroid colony formation.

Adult↗
PubMed1984

Chemotherapy resolves symptoms and reverses marrow fibrosis in myelofibrosis.

12 patients with symptomatic chronic myelofibrosis were treated with either busulphan or 6-thioguanine. Therapy was without significant side effects and resulted in a reduction in the size of liver and spleen and an improvement in well-being in all cases. In 7 patients the Hb value rose and the extent of marrow fibrosis was reduced in the 5 patients in whom bone marrow examination was repeated after treatment. Chemotherapy is an effective and safer alternative to splenectomy in patients with myelofibrosis with symptomatic anaemia, symptomatic splenomegaly or constitutional symptoms such as fever, weight loss and night sweats.

Aged↗