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At least 775 records · Page 43Linked to original sources
PubMed1989

Myelofibrosis with myeloid metaplasia following essential thrombocythaemia.

We report a male patient in whom a diagnosis of essential thrombocythaemia was made at the age of 25. The clinical course was characterised by recurrent thrombotic episodes during the first few years of the disease, followed by a relatively benign course. He was treated with 32P, nitrogen mustard and plateletpheresis. A transformation into myelofibrosis with myeloid metaplasia was revealed 20 years after ET diagnosis. The length of the disease and the 32P therapy are discussed as factors favouring this metamorphosis.

Humans↗
PubMed1988

Primary polycythaemia, essential thrombocythaemia and myelofibrosis--three facets of a single disease process?

Primary polycythaemia (PP), idiopathic myelofibrosis (MF), essential thrombocythaemia (ET) and chronic granulocytic or myeloid leukaemia (CGL) are clonal disorders of the pluripotent haemopoietic stem cells. We have studied granulocyte, megakaryocyte and erythroid progenitors from the peripheral blood of 7 patients with PP, 9 with ET, 19 with MF and 6 with CGL in order to characterise similarities and differences at the committed progenitor cell level. Spontaneous megakaryocytic and erythrocytic growth was characteristic of MF, PP and ET but was not seen in CGL. Circulating erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitors were markedly increased in MF and CGL, less raised in ET and closest to normal in PP. Erythropoietin-independent erythroid bursts (EIBFU-E) grew from the blood of patients with MF, PP and ET but spontaneous growth of megakaryocytes occurred in only MF and ET. These results suggest a progression of increasing abnormality from PP, where EIBFU-E occurred with relatively normal numbers of circulating progenitors, to ET where both EIBFU-E and megakaryocyte precursors regularly occur with elevated numbers of progenitors, to MF where spontaneous BFU-E, CFU-Mk and CFU-GM occur at high levels.

Colony-Forming Units Assay↗
PubMed1987

Chromosome abnormalities in myelofibrosis.

Cytogenetic analysis was performed on megakaryocyte-enriched cell fractions obtained by separation on discontinuous Percoll gradients from blood, bone marrow, and ascitic fluid of 12 patients with myelofibrosis with myeloid metaplasia (MMM). The most common abnormalities appeared to involve chromosomes 1, 3, 7, 8, 11, 13, 21 and 22. Although no specific chromosome rearrangements were observed in megakaryocytic fractions from different tissues of the patients with MMM, the presence in one case of a 3q-abnormality restricted to polyploid metaphases only, and of a 3q paracentric inversion in another patient, seems to confirm a close relationship between the involvement of chromosome 3 and dysplastic thrombopoiesis.

Chromosome Aberrations↗
PubMed1985

Myelofibrosis, splenomegaly, and portal hypertension.

A patient with chronic myelofibrosis and massive splenomegaly developed portal hypertension with haematemesis occurring from radiologically proven oesophageal varices. Transjugular liver biopsy showed only myeloid metaplasia, and radiological evaluation of the portal vascular system was undertaken to establish a diagnosis of hyperkinetic portal hypertension as a basis for therapeutic splenectomy. The alternative and rare situation of splenic and portal vein occlusion was demonstrated and therefore removal of the spleen was not an appropriate procedure for relief of portal hypertension. The variceal bleeding was successfully controlled with injection sclerotherapy.

Esophageal and Gastric Varices↗
PubMed1985

Idiopathic myelofibrosis complicated by lymphoma. Report of two cases.

2 cases of diffuse large-cell non-Hodgkin's lymphoma developing in conjunction with idiopathic myelofibrosis are described. In neither case could any predisposition to neoplastic transformation be discerned. The possible pathogenetic implications of this association are discussed, and a brief literature review of the relationship between myeloproliferative and lymphoproliferative disease is presented.

Adult↗
PubMed1979

Clonal evolution of marker chromosomes in a case of myelofibrosis with myeloid metaplasia and myeloblastic transformation.

The diverse spectrum of acquired chromosome abnormalities in a female patient with myelofibrosis and myeloid metaplasia is described. A sequence of karyotypic evolution involving a ring chromosome is postulated. The terminal clinical picture was unusual in that there was obstructive renal failure from extramedullary myeloblastic transformation and infiltration of the bladder, and this was also present in other sites. Initially neutrophils showed low alkaline phosphatases activity but latterly two distinct populations in which cells had either high activity or none.

Alkaline Phosphatase↗
PubMed1978

Different composition of the erythropoietic tissue in bone marrow, spleen and liver in myelofibrosis.

Aspirates from bone marrow, spleen and liver were analysed in 10 untreated patients with idiopathic myelofibrosis (MF). The proportion of erythroblasts was higher in the spleen and the liver than in the bone marrow. The mitotic indices of the erythropoietic precursor cells were subnormal in the extramedullary sites and significantly lower in the liver compared with the spleen. There was a "shift to the left" within the liver erythropoiesis and a significant megaloblastosis in the spleen. The same tendencies have formerly been found in patients with chronic myeloid leukemia and it is suggested that the discrepancies may be due to differences in the microenvironment of the erythropoietic cells.

Adult↗
PubMed1995

Sweet's syndrome with myelofibrosis and leukemia: partial response to interferon.

Sweet's syndrome with malignancy or acute neutrophilic dermatosis (AND) is an unusual cutaneous disorder seen most commonly in association with acute myelogenous leukemia. A large majority of patients with AND and malignancy have neoplasms of hematopoietic, plasma cell or lymphoid nature. The patient reported here had myelofibrosis, chronic myelogenous leukemia and Sweet's syndrome. The individual lesions responded to intralesional interferon-alpha 2, which has not to our knowledge been reported previously. This result, however, was not as great as the response of AND to intralesional steroid injections.

Aged↗
PubMed2002

Idiopathic myelofibrosis with prominent postsplenectomy erythroblastosis terminating in acute myeloid transformation.

Idiopathic myelofibrosis is a myeloproliferative disease with poor prognosis and without sufficient therapy. Acute leukemic transformation occurs in 15% of patients. The authors report the case of a 63 year old myelofibrotic patient treated with splenectomy. During the clinical course they observed unusually prominent and persistent erythroblastosis in the peripherial blood. After a two years long, relatively stable period the disease terminated in acute myeloid leukemia.

Acute Disease↗
PubMed1997

Idiopathic myelofibrosis (agnogenic myeloid metaplasia) in a marmoset (Callithrix jacchus): hematologic and histopathologic changes.

Idiopathic myelofibrosis (IMF), or agnogenic myeloid metaplasia, was diagnosed in a sexually mature male marmoset (Callithrix jacchus) based on the results of hematology and histopathologic evaluation of the bone marrow. The hematologic changes included pancytopenia, leukoerythroblastosis, anisocytosis, poikilocytosis, and giant platelets. Histopathologic evaluation of the bone marrow showed marked widespread fibrosis replacing hematopoietic cells and the presence of atypical megakaryocytes. In addition, slight multifocal osteolysis with an increase in serum alkaline phosphatase activity was observed. We believe this is the first report of IMF in a nonhuman primate species.

Animals↗
PubMed1997

Successful treatment of early secondary myelofibrosis in SLE with IVIG.

Myelofibrosis has been reported as a rare cause of pancytopenia in patients with autoimmune diseases. We describe a 54y old female patient who was admitted with severe anemia subsequently found to be due to marrow fibrosis. During the course of her hospitalization, relying both on her clinical symptoms as well as the results of a wide range of laboratory tests and diagnostic procedures, the diagnosis of systemic lupus erythematosus was established. The patient was treated with high dose steroids, but improvement of her clinical symptoms as well as normalization of her peripheral blood count were achieved only after high dose intravenous therapy with gamma globulin (IVIG) was instituted. Along with the improvement in the peripheral blood parameters normalization of the bone marrow architecture was recorded on a repeated bone marrow biopsy. IVIG therapy should be considered in extreme cases of bone marrow suppression in SLE.

Biopsy↗
PubMed2002

Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia.

In a phase 2 study, 23 patients with myelofibrosis with myeloid metaplasia were treated with imatinib mesylate at a constant dose of 400 mg/d. Treatment was held in 16 patients (70%), after 1 to 12 weeks, because of side effects (neutropenia, 6 patients; musculoskeletal pain, 5 patients; thrombocytosis, 4 patients; edema, 3 patients; diarrhea and hyperbilirubinemia, 1 patient). Including patients in whom retreatment at a reduced dose was possible, 11 patients (48%) were able to continue treatment beyond 3 months. None of the patients experienced a response in anemia, and only 2 had partial responses in splenomegaly. A greater than 50% increase in platelet count was documented in 11 (48%) patients, but not in those with baseline platelet counts of less than 100 x 10(9)/L. In vitro, imatinib mesylate caused variable degrees of growth suppression of myeloid and erythroid progenitors that unfortunately did not translate into clinical benefit.

Adult↗
PubMed2002

Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors.

Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by megakaryocyte hyperplasia and bone marrow fibrosis. Biologically, an autonomous megakaryocyte growth and differentiation is noticed, which contributes to the megakaryocyte accumulation. To better understand the molecular mechanisms involved in this spontaneous growth, we searched for genes differentially expressed between normal megakaryocytes requiring cytokines to grow and IMF spontaneously proliferating megakaryocytes. Using a differential display technique, we found that the immunophilin FKBP51 was 2 to 8 times overexpressed in megakaryocytes derived from patients' CD34(+) cells in comparison to normal megakaryocytes. Overexpression was moderate and confirmed in 8 of 10 patients, both at the mRNA and protein levels. Overexpression of FKBP51 in a UT-7/Mpl cell line and in normal CD34(+) cells induced a resistance to apoptosis mediated by cytokine deprivation with no effect on proliferation. FKBP51 interacts with both calcineurin and heat shock protein (HSP)70/HSP90. However, a mutant FKBP51 deleted in the HSP70/HSP90 binding site kept the antiapoptotic effect, suggesting that the calcineurin pathway was responsible for the FKBP51 effect. Overexpression of FKBP51 in UT-7/Mpl cells induced a marked inhibition of calcineurin activity. Pharmacologic inhibition of calcineurin by cyclosporin A mimicked the effect of FKBP51. The data support the conclusion that FKBP51 inhibits apoptosis through a calcineurin-dependent pathway. In conclusion, FKBP51 is overexpressed in IMF megakaryocytes and this overexpression could be, in part, responsible for the megakaryocytic accumulation observed in this disorder by regulating their apoptotic program.

Base Sequence↗
PubMed2002

Both B and T lymphocytes may be clonally involved in myelofibrosis with myeloid metaplasia.

A combination of magnetic cell sorting (MACS) and fluorescent in situ hybridization (FISH) techniques was used to detect clonal cytogenetic markers in different myeloid and lymphoid cell types of the peripheral blood from 4 patients with myelofibrosis with myeloid metaplasia (MMM) that was associated with either a 13q- or a 20q- karyotypic abnormality. Interphase cytogenetics studies demonstrated abnormal clonal FISH signal patterns in neutrophil, myeloid, erythroid, megakaryocyte, and B- and T-cell preparations in 3 of the 4 patients. In one patient, FISH results were within normal limits in T cells and slightly abnormal in B cells. In general, the percentage of abnormal nuclei was variable in both lymphocyte populations but always higher in B lymphocytes compared with T lymphocytes. The current study provides direct evidence for the clonal involvement of both B and T lymphocytes in MMM. A larger study is needed to clarify the relevance of the observed interpatient heterogeneity in clonal constitution.

Antigens, CD↗
PubMed2002

A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia.

Single-agent thalidomide (THAL) at "conventional" doses (> 100 mg/d) has been evaluated in myelofibrosis with myeloid metaplasia (MMM) based on its antiangiogenic properties and the prominent neoangiogenesis that occurs in MMM. THAL monotherapy at such doses produces approximately a 20% response rate in anemia but is poorly tolerated (an adverse dropout rate of > 50% in 3 months). To improve efficacy and tolerability, we prospectively treated 21 symptomatic patients (hemoglobin level < 10 g/dL or symptomatic splenomegaly) with MMM with low-dose THAL (50 mg/d) along with a 3-month oral prednisone (PRED) taper (beginning at 0.5 mg/kg/d). THAL-PRED was well tolerated in all enrolled patients, with 20 patients (95%) able to complete 3 months of treatment. An objective clinical response was demonstrated in 13 (62%) patients, all improvements in anemia. Among 10 patients who were dependent on erythrocyte transfusions, 7 (70%) improved and 4 (40%) became transfusion independent. Among 8 patients with thrombocytopenia (platelet count < 100 x 10(9)/L), 6 (75%) experienced a 50% or higher increase in their platelet count. In 4 of 21 patients (19%), spleen size decreased by more than 50%. Responses observed were mostly durable after discontinuation of the PRED. The dose of THAL in this study (50 mg/d) was better tolerated than the higher doses used in previous studies. Adverse events associated with corticosteroid therapy were mild and transient. Clinical responses did not correlate with improvements in either intramedullary fibrosis or angiogenesis. THAL-PRED is well tolerated and preliminarily appears to be a promising drug regimen for treating cytopenias in patients with MMM.

Adrenal Cortex Hormones↗