Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MYELOFIBROSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1988

Myelofibrosis in cats with myelodysplastic syndrome and acute myelogenous leukemia.

Bone marrow sections from 44 cats with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) were graded for reticulin content using light microscopic methods. Twenty-seven (61%) of the cats had slight to marked reticulin myelofibrosis. The association of myelofibrosis with possible pathogenetic factors, including megakaryocyte count, intramedullary lymphoid follicles, hemosiderin content, and FeLV antigenemia, was examined. No evidence was found that indicated a causal relationship between myelofibrosis and any of these factors.

Animals↗
PubMedDate not supplied

Myelofibrosis associated with severe vitamin D deficiency rickets.

Myelofibrosis is a rare disorder in childhood. In this report, we present the case of a 6-month-old infant with myelofibrosis due to severe vitamin D deficiency rickets. The characteristic clinical and laboratory findings of myelofibrosis improved rapidly after vitamin D therapy. In developing countries, nutritional rickets is still an important health problem. Rickets is not only a skeletal system-related disorder, it is also a systemic disorder. Rickets should be considered, therefore, as one of the conditions that can lead to severe haematological disorders in infants.

Bone and Bones↗
PubMed2002

Prominent role of TGF-beta 1 in thrombopoietin-induced myelofibrosis in mice.

Several studies suggest an implication of transforming growth factor-beta1 (TGF-beta1) in the promotion of myelofibrosis associated with hematopoietic malignancies, but the involvement of this cytokine is not fully investigated. To test directly the impact of TGF-beta1 in the pathogenesis of myelofibrosis, bone marrow stem cells from homozygous TGF-beta1 null (TGF-beta1(-/-)) and wild-type (WT) littermates were infected with a retrovirus encoding the murine thrombopoietin (TPO) protein and engrafted into lethally irradiated wild-type hosts for long-term reconstitution. Over the 4 months of follow-up, TPO levels in plasma were markedly elevated in both groups of mice, and animals typically developed a myeloproliferative syndrome characterized by thrombocytosis, leukocytosis, splenomegaly, increased numbers of progenitors in blood, and extramedullary hematopoiesis. Severe fibrosis was observed in spleen and marrow from all the mice engrafted with WT cells. In contrast, none of the mice repopulated with TGF-beta1(-/-) cells (chimerism > 70%) showed deposition of reticulin fibers at any time during the follow-up. In accordance with the development of fibrosis, latent TGF-beta1 levels in plasma and extracellular fluid of the spleen from mice engrafted with WT cells were increased 6-fold and 4-fold, respectively, over levels found in normal hosts, whereas no increase over baseline levels could be demonstrated in animals undergoing transplantation with TGF-beta1(-/-) cells. These data provide evidence that TGF-beta1 produced by hematopoietic cells is pivotal for the pathogenesis of myelofibrosis that develops in mice with TPO overexpression.

Animals↗
PubMed2002

Development of myelofibrosis in mice genetically impaired for GATA-1 expression (GATA-1(low) mice).

The phenotype induced by the GATA-1(low) (neodeltaHS) mutation is here further characterized by analyzing the hemopoietic system during the aging (up to 20 months) of a GATA-1(low) colony (135 mutants and 40 normal littermates). Mutants expressed normal hematocrit values (Hct = 45.9 +/- 4.0) until 12 months but became anemic from 15 months on (Hct = 30.9 +/- 3.9; P <.05). Anemia was associated with several markers of myelofibrosis such as the presence of tear-drop poikilocytes and progenitor cells in the blood, collagen fibers in the marrow and in the spleen, and hemopoietic foci in the liver. Semiquantitative reverse transcription-polymerase chain reaction showed that growth factor genes implicated in the development of myelofibrosis (such as osteocalcin, transforming growth factor-beta1, platelet-derived growth factor, and vascular endothelial growth factor) were all expressed in the marrow from the mutants at higher levels than in corresponding normal tissues. The GATA-1(low) mutants experienced a slow progression of the disease because the final exitus was not observed until at least 15 months with a probability of survival more favorable than that of W/Wv mice concurrently kept in the animal facility (P <.001, by Kaplan-Meier analysis). In conclusion, impaired GATA-1 expression may contribute to the development of myelofibrosis, and the GATA-1(low) mutants may represent a suitable animal model for the human disease that may shed light on its pathogenesis.

Anemia↗
PubMed2006

Monitoring of the JAK2-V617F mutation by highly sensitive quantitative real-time PCR after allogeneic stem cell transplantation in patients with myelofibrosis.

The JAK2-V617F mutation occurs in about 50% of patients with myelofibrosis and might be a reliable marker to monitor residual disease after allogeneic stem cell transplantation. We describe a new, highly sensitive (>or= 0.01%) real-time polymerase chain reaction (PCR) to monitor and quantify V617F-JAK2-positive cells after dose-reduced allogeneic stem cell transplantation. After 22 allogeneic stem cell transplantation procedures in 21 JAK2-positive patients with myelofibrosis, 78% became PCR negative. In 15 of 17 patients (88%), JAK2 remained negative after a median follow-up of 20 months. JAK2 negativity was achieved after a median of 89 days after allograft (range, 19-750 days). A significant inverse correlation was seen for JAK2 positivity and donor-cell chimerism (r:-0.91, P<.001). Four of 5 patients who never achieved JAK2 negativity fulfilled during the entire follow-up all criteria for complete remission recently proposed by the International Working Group, suggesting a major role for JAK2 measurement to determine depths of remission. In one case, residual JAK2-positive cells were successfully eliminated by donor lymphocyte infusion. In conclusion, allogeneic stem cell transplantation after dose-reduced conditioning induces high rates of molecular remission in JAK2-positive patients with myelofibrosis, and quantification of V617F-JAK2 mutation by real-time PCR allows the detection of minimal residual disease to guide adoptive immunotherapy.

Adult↗
PubMed2005

Pathogenesis of myelofibrosis with myeloid metaplasia.

The primary disease process in myelofibrosis with myeloid metaplasia (MMM) is clonal myeloproliferation with varying degrees of phenotypic differentiation. This is characteristically accompanied by secondary intramedullary collagen fibrosis, osteosclerosis, angiogenesis, and extramedullary hematopoiesis. Modern clonality studies have confirmed the multipotent stem-cell origin of the neoplastic process in MMM. The nature of the specific oncogenic mutation(s) is currently being unraveled with the recent discovery of an association between a somatic point mutation of JAK2 tyrosine kinase (V617F) and bcr/abl-negative myeloproliferative disorders, including MMM. The pathogenetic mechanisms that underlie the secondary bone marrow stromal changes in MMM are also incompletely understood. Mouse models of this latter disease aspect have been constructed by either in vivo overexpression of thrombopoietin (TPOhigh mice) or megakaryocyte lineage restricted underexpression of the transcription factor GATA-1 (GATA-1low mice). Gene knockout experiments using such animal models have suggested the essential role of hematopoietic cell-derived transforming growth factor beta1 in inducing bone marrow fibrosis and stromal cell-derived osteoprotegerin in promoting osteosclerosis. However, experimental myelofibrosis in mice does not recapitulate clonal myeloproliferation that is fundamental to human MMM. Other cytokines that are implicated in mediating myelofibrosis and angiogenesis in MMM include basic fibroblast, platelet-derived, and vascular endothelial growth factors. It is currently assumed that such cytokines are abnormally released from clonal megakaryocytes as a result of a pathologic interaction with neutrophils (eg, emperipolesis). This latter phenomenon, through neutrophil-derived elastase, could also underlie the abnormal peripheral-blood egress of myeloid progenitors in MMM.

Animals↗
PubMedDate not supplied

Primary myelofibrosis terminating in megakaryoblastic crisis.

Primary myelofibrosis terminating in megakaryoblastic crisis is uncommon. A case with this condition is reported. The patient, a 62-year-old female, having had primary myelofibrosis for 13 years and a splenectomy 4 years before, was admitted because of high fever, hepatomegaly, thrombocythemia and leukocytosis. On admission, blasts appeared in the peripheral blood and thereafter gradually increased in number. The blasts were proven to be of megakaryocytic lineage. To our knowledge this is the third case of primary myelofibrosis terminating in megakaryoblastic crisis to be reported in Japan.

Female↗
PubMed2000

Idiopathic myelofibrosis developing isolated granulocytic sarcoma with der (1;7)(q10; p10) after splenectomy and finally transforming to acute myelogenous leukemia.

A 47-year-old female with idiopathic myelofibrosis developed isolated granulocytic sarcoma with der (1; 7)(q10; p10) after splenectomy, followed by acute myelogenous leukemia. The patient had myelofibrosis since 22 years of age, received splenectomy at 47 years, and developed isolated submandibular granulocytic sarcoma, 8 months later. Although the initial tumor disappeared after irradiation, recurrent tumors selectively appeared in the areas of operative scars. She subsequently developed blastic transformation with der (1; 7)(q10; p10), and the blasts were refractory to different chemotherapy. This case is very rare in the following aspects: the onset of myelofibrosis occurred at a relatively young age; isolated granulocytic sarcoma after splenectomy preceded the transformation to acute leukemia; and the subcutaneous tumors developed in areas of operative scars.

Chromosomes, Human, Pair 1↗
PubMed1995

Platelet derived growth factor expression, myelofibrosis and chronic myelogenous leukemia.

CML is often associated with myelofibrosis, and fibrosis in the accelerated phase is one of the diagnostic criteria for this accelerated phase. In this review, the mechanism of myelofibrosis associated with CML is discussed with emphasis on the cell origin of the production and release of platelet derived growth factor (PDGF) and its interaction with marrow fibroblasts. In the initial stage of myelofibrosis in chronic phase CML, atypical small megakaryocytes might leak PDGF, possibly PDGF-AB, together with other growth factors. As the clinical phase of the disease progresses to accelerated or blastic phase, a larger quantity of PDGF-AB or PDGF-BB might be secreted from blastic cells with myeloid phenotype. In addition some fibroblasts may be attracted by the PDGF and proliferate, and deposit collagen as well as fibronectin in the bone marrow stroma.

Blast Crisis↗
PubMed1996

Serum G-CSF levels in primary myelofibrosis and chronic neutrophilic leukemia as estimated by the highly sensitive chemiluminescence enzyme immunoassay (CLEIA).

We previously reported that serum granulocyte colony stimulating factor levels of chronic myelogenous leukemia patients in chronic phase (CP) are significantly lower than those of healthy persons or other hematological malignancies as assessed by chemiluminescence enzyme immunoassay (CLEIA). In this study, we clarify the difference in serum G-CSF levels between patients with primary myelofibrosis (PMF, myelofibrosis with myeloid metaplasia; MMM) and those with secondary myelofibrosis caused by several hematological disorders, using the same highly sensitive CLEIA method. It is clearly demonstrated that serum G-CSF levels of the patients with PMF and chronic neutrophilic leukemia (CNL) are extremely low, similar to those in patients with CML in CP in this study. From these data, it is speculated that the abnormal proliferation of granulocytes in PMF and CNL may not be due to the stimulation by G-CSF, and that a negative feedback mechanism might exist between peripheral granulocytes and serum G-CSF.

Biomarkers↗
PubMed1999

Trisomy 13 is associated with poor prognosis in idiopathic myelofibrosis with myeloid metaplasia.

We report a case of idiopathic myelofibrosis with trisomy 13 as the sole clonal aberration, as demonstrated by metaphase cytogenetics. The clinical course was especially poor in this case, with death in blast crisis occurring within two weeks from diagnosis. The dismal outcome bears striking similarity to two previous cases of idiopathic myelofibrosis and trisomy 13 reported in the literature. Therefore trisomy 13 may be a predictor of a rapidly fatal outcome in this otherwise indolent disease. Fluorescence in situ hybridisation (FISH) with a chromosome 13 specific probe may enhance the detection of this aberration, since only 50% of cases of idiopathic myelofibrosis are karyotyped successfully using conventional techniques.

Aged↗
PubMedDate not supplied

Subcutaneous panniculitic T-cell lymphoma developing in a child with idiopathic myelofibrosis.

PURPOSE: Subcutaneous panniculitic T-cell lymphoma is reported in a child with idiopathic myelofibrosis. Both disease entities are rarely seen in children. PATIENT AND METHODS: A girl aged 5 years and 9 months had pancytopenia and severe constitutional symptoms. Idiopathic myelofibrosis was subsequently diagnosed. RESULTS: A transient response was achieved after treatment with a course of high-dose methylprednisolone therapy. However, proptosis and skin nodules developed during tapering of steroid therapy. A computed tomography scan of the orbit also revealed a mass lesion in the right lacrimal gland region. A skin biopsy specimen showed a subcutaneous panniculitic T-cell lymphoma. The clinical course was marked by high fever, profound pancytopenia, massive gastrointestinal bleeding, and severe, recurrent infections. Her condition rapidly deteriorated, and she died from polymicrobial sepsis 4 months after her initial examination. CONCLUSIONS: Subcutaneous panniculitic T-cell lymphoma is a distinctive clinicopathologic entity that is rarely seen in children. The association of myelofibrosis and peripheral T-cell lymphoma as seen in this has been rarely reported.

Child↗
PubMed2000

Bone marrow histochemical studies of fibrogenic cytokines and their receptors in myelodysplastic syndrome with myelofibrosis and related disorders.

Cellular and extracellular alterations of various fibrogenic cytokines have been described in a number of different chronic myeloid disorders that are associated with myelofibrosis. However, the available information related to both myelodysplastic syndrome with myelofibrosis (MDS-f) and bone marrow histochemical analysis is limited. In the current study, bone marrow immunohistochemical staining for platelet-derived growth factor, transforming growth factor (TGF)-beta, basic fibroblast growth factor (bFGF), and their receptors was performed in 9 patients with MDS-f, 9 patients with essential thrombocythemia (ET), 8 patients with 5q- syndrome, and 5 healthy control subjects. In addition, TGF-beta1 messenger RNA (mRNA) analysis was performed in 5 patients, each with MDS-f, myelofibrosis with myeloid metaplasia (MMM), polycythemia vera (PV), ET, and immune thrombocytopenic purpura, and in healthy control subjects. In general, protein and transcript expression patterns were similar to normal patterns and not significantly different among the various disease groups. The only exception was a reduced concentration of bFGF-expressing stromal cells in patients with PV, ET, and MMM.

Adult↗
PubMedDate not supplied

[Myeloid leukemia with myelofibrosis (author's transl)].

Myelofibrosis is observed in 1/5 of the cases of C.M.L. It consists of reticulin fibers with few collagen and no osteosclerosis. It involves signs which usually indicate the extension of the myelosis to other organs and other types of cells: hepatosplenomegaly, erythroblastosis, thrombocytemia. Its prognosis is always bad. In one third of the cases, myelofibrosis develops early, and in two third it is late. Chimiotherapy is not responsible for it. These forms of C.M.L. with myelofibrosis appear as a special type of myeloproliferative disorder apart from the true C.M.L. and the true osteomyelofibrosis.

Alkaline Phosphatase↗
PubMed2004

[Complete regression of bone marrow fibrosis following allogeneic peripheral blood stem cell transplantation in a patient with idiopathic myelofibrosis].

The authors present a case of a 47-year-old man with idiopathic myelofibrosis. The diagnosis of myelofibrosis was made in 1981. Because of progression of the disease and failure of hematopoiesis in 2002, allogeneic peripheral blood stem cell transplantation was performed; the donor was an HLA identical relative. Six months after transplantation, trephin biopsies were made and a complete regression of bone marrow fibrosis was documented. It is the first case of this treatment for idiopathic myelofibrosis in the University Hospital in Hradec Králové.

Adult↗
PubMed2005

Myelofibrosis and vitamin D deficient rickets--a rare association.

Myelofibrosis is a rare hematological condition in infancy. We report a case of a 6-month-old infant who was diagnosed to have myelofibrosis due to Vitamin D deficient rickets. This rare association of myelofibrosis and rickets is discussed here with a review of relevant literature.

Fatal Outcome↗
PubMed1991

[Acute malignant myelofibrosis. Report of 3 cases].

This report describes three cases of acute malignant myelofibrosis characterized by pancytopenia, absence of splenomegaly, bone marrow fibrosis with an immature cell proliferation and rapidly fatal outcome. The authors investigated the origin of blast cells with the use of immunohistochemical markers on paraffin embedded material with anti-factor VIII, BNH9 and anti-lysozyme. They studied the expression of megakaryoblastic, erythroblastic and myeloblastic differentiation in these cells. They demonstrated the heterogeneity of blast cells which are capable of differentiating along the three hematologic cell lines. The morphometric study showed the mutilating or systematized character of myelofibrosis. The increase in reticulin fiber density compared with normal bone marrow was not significantly different from two other types of myelofibrosis. It would be interesting to correlate a quantitative parameter with the course of this disease in order to evaluate the prognosis and the treatment.

Acute Disease↗
PubMed1990

Primary myelofibrosis in children: report of 4 cases.

From 1982 to 1985, four cases of primary myelofibrosis were diagnosed in our department. Three were boys and one was a girl. Their ages ranged from 7 months to 15 years. The diagnosis was made based on anemia, leukoerythroblastic change and presence of giant platelets in the peripheral blood, and a bone marrow biopsy showing myelofibrosis. Most of them had anemia, fever, and hepatosplenomegaly on admission. The anemia was severe and refractory to repeated transfusions and steroid therapy in 3 out of the 4 cases. Splenectomy was performed in 1 case, but without satisfactory results. The clinical course and blood pictures in one case resembled leukemia of megakaryocyte lineage (M7), but results of marker studies of the blast cells ruled out the possibility of M7. Three of them underwent leukemic transformation within 2 years and died soon after. The other one died of sepsis 2 weeks after diagnosis. Myelofibrosis in childhood occurs rarely, however, when it does, it always runs a rapid and fatal course.

Adolescent↗