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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis of an essential thrombocytosis is demonstrated in this presentation of a well-looking 53 year old man who had a five-year history of increasing facial asymmetry as evidenced by deviation of his mandible to the right and malocclusion. The enlarged mandibular condyle was the first manifestation of his underlying myeloproliferative disorder. His management will be discussed. Neoplastic diseases of the multipotent haematopoietic stem cells result in four major diseases: chronic myelogenous leukaemia (CML); polycythaemia vera (PV); agnogenic myeloid metaplasia with myelofibrosis (AMM/MF); essential thrombocytosis (ET). CML: demonstrates increased production of neutrophils and marked splenomegaly. It is divided into a chronic phrase typified by hyperplasia of mature bone marrow elements and a blastic or acute phase which evolves into a proliferation of immature marrow elements and can develop into acute myelogenous leukaemia. PV: associated with increased production of all myeloid cells but dominated by increased red blood cells with splenomegaly. AMM/MF: allows the neoplastic stem cells to proliferate and lodge in multiple sites outside the bone marrow. Splenomegaly and fibrosis of marrow spaces also occurs. ET: resulting in a markedly elevated platelet count in the absence of a recognizable stimulus. Treatment revolves around measures to maintain hydration, to relieve arthralgias, to prevent thrombotic episodes, and to prevent infections.
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PMID:A review of myeloproliferative disease with presentation in the head and neck region. 1089 23

During fetal development, the spleen is a major hemopoietic organ. In the adult human, this task is relinquished to the bone marrow. However, under the stress of certain pathologic conditions, extramedullary hemopoiesis may again occur in the spleen. This is especially true for diseases of the marrow, in particular, myeloproliferative disorders such as agnogenic myeloid metaplasia, which is associated with severe fibrosis of the marrow space. At the same time, the spleen sequesters blood cells and contributes to peripheral blood cytopenias, which may improve following splenectomy. However, success is unpredictable, and the operative mortality of splenectomy is on the order of 10%. As a growing number of patients undergo hemopoietic stem cell transplantation as definitive therapy for myelofibrosis, the decision on splenectomy has additional ramifications since the spleen plays an important role in the kinetics of engraftment of donor cells and in immune reconstitution. We conclude from our analysis of available information that the benefit of splenectomy is difficult to predict, although after transplantation splenectomized patients have faster hemopoietic recovery. It appears that the most important indication for splenectomy in these patients is the relief of symptoms from massive spleen enlargement.
Leukemia 2001 Mar
PMID:Pros and cons of splenectomy in patients with myelofibrosis undergoing stem cell transplantation. 1123 72

Polycythaemia vera (PV) and essential thrombocytosis (ET) are clinically characterised by non-specific neurologic symptoms, peripheral circulatory disturbances (acrocyanosis, wounds, erythromelalgia) or abdominal symptoms. The treatment of PV includes phlebotomy, antiaggregation and cytoreduction. In ET, the primary treatment is also low-dose aspirin except for patients presenting with a haemorrhagic diathesis. Hydroxyurea may be associated with an increased risk of acute leukaemia or myelodysplasia. Therefore alpha-interferon and anagrelide should be considered in younger patients. Early cytoreductive therapy is advocated in patients with idiopathic myelofibrosis (IMF) to inhibit further progression of bone marrow fibrosis and further expansion of myeloid metaplasia in the spleen and liver. Treatment with androgens (danazol) and glucocorticoids may improve severe anaemia and thrombocytopenia. In younger patients, allogeneic bone marrow transplantation should be considered.
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PMID:[The chronic Philadelphia chromosome-negative myeloproliferative syndrome II. Clinical findings, diagnostics and treatment]. 1137 60

An increase of angiogenesis has been shown in idiopathic myelofibrosis with myeloid metaplasia (MMM) by microvessel density count method but evaluation of circulating angiogenic factors is still incomplete. In 31 patients affected by MMM and in 12 healthy subjects we evaluated the serum levels of VEGF (vascular endothelial growth factor) and correlated VEGF with clinical and laboratory features of disease. We found that MMM patients had circulating VEGF concentrations much higher than controls (Median 1208 ng/ml vs 138 ng/ml, P < 0.0001). No correlation was found between VEGF and Hb, WBC, PLT, LDH, creatinine, bone marrow cellularity, fibrosis, splenomegaly, hepatomegaly, and therapy. However, in the subgroup of patients with a normal or low VEGF concentration, a direct correlation between VEGF and platelet count (r = 0.90, P = 0.002) was detected. Moreover, patients with a platelet count < 300 x 10(9)/l had VEGF serum levels lower than patients with a higher PLT count (median VEGF 864 vs 1557 pg/ml, P = 0.001). In six patients and in eight controls we also had the opportunity to measure VEGF in the plasma and we calculated that VEGF concentration was much higher in platelet-rich than in platelet-poor plasma and that platetets of MMM patients contained four times more VEGF than those of healthy controls. These results indicate that VEGF is overproduced in MMM, thus confirming an increased angiogenic activity. Platelets are probably a major source of VEGF in MMM but not the only one.
Leukemia 2001 Jun
PMID:Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis. 1141 86

The role of angiogenesis for the progressive growth and metastatic process of tumours is well established. What is not clear, though, is the clinical prognostic significance of the angiogenic factors in malignant haematological diseases. In this study, we have assessed the plasma and serum levels of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) in 55 patients affected by chronic myeloproliferative disorders (CMD). This series included 25 patients with essential thrombocythemia (ET), 10 patients with chronic myelocytic leukaemia (CML), 14 patients with polycythemia vera (PV), and 6 patients with primary myelofibrosis (MF), and they were compared to 20 healthy control subjects. In all patients the plasma VEGF concentration was significantly increased to the healthy control group (P < 0.004). The highest concentrations were found in the patients with ET (178.25 +/- 125.22 pg/ml). The VEGF levels were significantly higher in CMD patients with vascular complications than those in CMD patients without complications (P < 0.01). The b-FGF serum levels also appeared to be significantly higher in almost all the CMD patients compared to the control group (P < 0.07). A significant correlation was found between the VEGF levels and the platelet count in the ET patients and the spleen index in the CML patients. VEGF level, in this study, is associated with increased risk of thrombotic complications. There is evidence of increased levels of soluble angiogenic factors in malignant haematological disorders, but their contribution to the progression of diseases is yet unclear.
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PMID:Soluble angiogenic factors: implications for chronic myeloproliferative disorders. 1189 1

Increased neoangiogenesis has been reported in myelofibrosis with myeloid metaplasia (MMM). Thus we studied the effects of thalidomide, an antiangiogenic drug, in 12 MMM patients. Before treatment, all the cases showed a significantly increased micro-vessel density (MVD); in all eight tested cases bFGF and VEGF plasma levels were higher than controls. All patients presented disease progression in the last 3 months with standard therapy, regarding splenomegaly, anemia and/or thrombocytopenia and/or hyperleukocytosis. Thalidomide was administered at daily doses increasing from 100 to 600 mg. Eleven out of 12 patients were evaluable. No progression of disease was seen during the treatment in any case. In particular, spleen size decreased in 7/11 patients, anemia improved in 3/4 (two are now transfusion independent), thrombocytopenia in 2/2 and hyperleukocytosis in 2/5 patients. Side-effects were frequent, although not severe. After treatment, VEGF and bFGF plasma levels varied widely and in selected cases decreased. In particular, VEGF and/or bFGF decreased in 4/5 responders and in 1/3 non-responders. Moreover, MVD significantly decreased in all the responders evaluated after treatment. We conclude that thalidomide is a feasible therapy in MMM patients and looks promising at least to control the growth progression of disease.
Leukemia 2002 Sep
PMID:Clinical efficacy and antiangiogenic activity of thalidomide in myelofibrosis with myeloid metaplasia. A pilot study. 1220 Jun 71

Alterations of the N-ras oncogene and p53 tumor suppressor gene have been demonstrated to play an important role in pathogenesis of hematological malignancies. We simultaneously investigated genetic lesions of both genes in bone marrow cells from 64 Japanese patients with myeloproliferative disorders (MPD), including polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (MF), by direct sequencing analysis. No mutations of the N-ras gene were detected in any cases. Two patients, one with chronic neutrophilic leukemia derived from PV and one with acute mylogenous leukemia derived from ET, exhibited three mutations of the p53 gene. Among them, two were missense mutations in exon 5 or 7 and one was a deletion in exon 5. All samples in chronic phase or from MF were devoid of mutations in both genes. These data suggested that disruptions of both genes are extremely rare in MPD in chronic phase and that loss of functions in the p53 gene could be involved in progression of MPD such as PV and ET.
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PMID:N-ras and p53 gene mutations in Japanese patients with myeloproliferative disorders. 1235 15

R115777 is an orally bioavailable farnesyltransferase inhibitor (FTI) that has displayed encouraging activity in patients with acute myeloid leukemia. To determine whether R115777 might exert similar activity in myelofibrosis with myeloid metaplasia (MMM), we evaluated its effects on circulating myeloid progenitor cells from patients with MMM (n=25) using in vitro colony-forming assays. The median R115777 concentrations that inhibited colony formation by 50% were 34 and 2.7 nM for myeloid and megakaryocytic colonies from MMM patients, respectively. Progenitors from normal controls and patients with other myeloproliferative disorders demonstrated similar sensitivity. Since the ras polypeptides are one putative target of FTIs, the potential role of ras effectors was examined by incubating parallel progenitor assays with the phosphatidyl-inositol-3 (PI-3) kinase inhibitor LY294002 and the mitogen-activated protein kinase 1 inhibitor PD98059. MMM progenitor colonies (n=7) were highly sensitive to LY294002 but not to PD98059, implying that the PI-3 kinase pathway may be critical for survival and proliferation of these cells. In addition to indicating that MMM progenitors are sensitive to clinically achievable R115777 concentrations in vitro, these results provide a potential explanation for the thrombocytopenia observed with R115777 during the treatment of other hematologic malignancies.
Leukemia 2003 May
PMID:In vitro antiproliferative activity of the farnesyltransferase inhibitor R115777 in hematopoietic progenitors from patients with myelofibrosis with myeloid metaplasia. 1275 Jun 96

The aim of the study was an estimation of the histomorphometry of megakaryocytes (MK) in bone marrow in selected myeloproliferative and lymphoproliferative diseases. Bone marrow specimens were obtained by trephine biopsies from 41 patients with polycythaemia rubra vera (PV), idiopathic myelofibrosis (MF), chronic lymphocytic leukaemia (CLL), hairy cell leukaemia (HCL) and diffuse large B-cell lymphoma (L). Morphometric evaluation was performed using a standard program set MicroImage (OLYMPUS). The greatest number of typical nucleated MK, "naked" nuclei, anucleated cytoplasmic fragments and the largest area were found in PV. The circular deviation factor of MK and their nuclei increased in all cases. The greatest number of clusters was observed in PV and HCL. A significant increase in the number of dysplastic and "naked" nuclei of MK was noted in all selected haematological diseases. The presence of neoplastic cells in bone marrow increased the morphological changes in MK. Quantitative and morphometrical significant differentiation of MK in separate microscopic field in the same slides confirms the necessity of performing trephine biopsies in each patient with haematological disorders.
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PMID:Histomorphometric study of megakaryocytes in bone marrow in selected myeloproliferative and lymphoproliferative diseases. 1276 78

The new WHO classification is based on the principles of REAL classification of lymphoma and expands to myeloid, mast cell and histiocytic/dendritic neoplasms. The distinct diseases are defined according to a combination of morphology, immunophenotype, genetic features, and clinical syndromes, and the cell origin is postulated. Lymphatic leukemia is included in lymphoma. The lymphoid malignancies are grouped into B cell lymphoma, T/NK cell lymphoma and Hodgkin lymphoma, and the myeloid neoplasm are grouped into 4 categories; chronic myeloproliferative diseases(chronic myelogeneous leukemia, polycythemia vera, chronic idiopathic myelofibrosis, essential thrombocythemia etc.), myelodysplastic/myeloproliferative diseases (chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia etc.), myelodysplastic diseases(perfactory anemia, refractory anemia with ringed sideroblasts etc.) and acute myeloid leukemia.
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PMID:[Malignant lymphoma and leukemia concepts in new WHO classification]. 1367 44


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