UMLS:C0023473 - FACTA Search

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Query: UMLS:C0023473 (chronic myeloid leukemia)
18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocytic sarcoma (GS) occurs in patients with chronic myeloproliferative disorders as well as in patients with acute myeloid leukemia (AML). These tumorous masses can occur anywhere in the body and have to be differentiated from lymphoma, carcinoma or infectious processes. We report the results of fine-needle aspiration cytology (FNAC) in 26 patients with GS. Seventeen patients suffered from AML and 9 from chronic myeloid leukemia (CML) blast crisis. In 5 patients with AML, GS was the initial presentation of hematological malignancy, in the remaining 21 patients, FNAC confirmed relapse of AML or extramedullary blast crisis of CML. In 8 patients, GS was located in the skin, in 17 in the lymph node and in another patient in the spinal canal. This study demonstrates the clinical utility and diagnostic accuracy of FNAC in the evaluation of GS from multiple sites.
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PMID:Diagnosis of granulocytic sarcoma by fine-needle aspiration cytology. 1083 54

A retrospective study of 126 patients with extreme thrombocytosis (defined as a platelet count > or = 1,000 x 10(9)/L) was performed during a five-year period (June 1994-June 1999). The aim of this study was to determine the etiology and to evaluate the clinical consequences of extreme thrombocytosis. Seventy patients (55.5%) had reactive thrombocytosis (RT) with an age range of 43 +/- 2.2 years, 56 (44.5%) had chronic myeloproliferative disorders (MPD) with an age range of 53 +/- 2.4 years. Underlying causes of RT were malignancy (25/70 or 35.7%), infection (16/70 or 22.9%), postsplenectomized beta-thalassemia/Hb E (11/70 or 15.7%), inflammation (12/70 or 17.1%), iron deficiency anemia (6/70 or 8.6%). Duration post splenectomy in our beta-thalassemia/Hb E patients ranged from 4 months to 21 years, with a median of 10 years. Subtypes of our MPD cases were chronic myeloid leukemia (30/56 or 53.6%), essential thrombocytosis (18/56 or 32.1%), polycythemia vera (4/56 or 7.1%), agnogenic myeloid metaplasia (3/56 or 5.4%) and unclassified MPD (1/56 or 1.8%). Bleeding and thrombotic tendency were respectively noted in 7 (12.5%) and 2 (3.6%) of MPD patients. Two patients of the MPD group (3.6%) experienced both bleeding and thrombotic episodes. One patient (1.4%) of the RT group developed vasculitis-associated thrombosis. However, none of the patients in the RT group had bleeding complications. Extreme thrombocytosis was not a rare condition in a university hospital population, and bleeding and/or thrombotic complication was more common in the MPD group.
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PMID:Etiology and incidence of thrombotic and hemorrhagic disorders in Thai patients with extreme thrombocytosis. 1086 14

Clinical, morphological and cytogenetic investigations were done in those patients with leukocytosis having become victims of the Chernobyl catastrophe. Of these (n = 10), six patients demonstrated chromosomal abnormalities. In the study made at a later date in six patients with cytogenetic abnormalities, five patients were found to have chronic myeloproliferative disorders, with four cases presenting with chronic myeloid leukemia and one patient having osteomyelofibrosis.
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PMID:[The characteristics of the pre- and leukemic stages of chronic myeloproliferative diseases in persons suffering as a result of the Chernobyl catastrophe]. 1087 66

The pathogenesis of polycythemia vera (PV), a disease involving a multipotent hematopoietic progenitor cell, is unknown. Thrombopoietin (TPO) is a newly characterized hematopoietic growth factor which regulates the production of multipotent hematopoietic progenitor cells as well as platelets. To evaluate the possibility that an abnormality in TPO-mediated signal transduction might be involved in the pathogenesis of PV, we examined TPO-induced protein tyrosine phosphorylation using platelets as a surrogate model system. Platelets were isolated from the blood of patients with PV as well as from patients with other chronic myeloproliferative disorders and control subjects. Impaired TPO-mediated platelet protein tyrosine phosphorylation was a consistent observation in patients with PV as well as those with idiopathic myelofibrosis (IMF), in contrast to patients with essential thrombocytosis, chronic myelogenous leukemia, secondary erythrocytosis, iron deficiency anemia, hemochromatosis, or normal volunteers. Thrombin-mediated platelet protein tyrosine phosphorylation was intact in PV platelets as was expression of the appropriate tyrosine kinases and their cognate substrates. However, expression of the platelet TPO receptor, Mpl, as determined by immunoblotting, chemical crosslinking or flow cytometry was markedly reduced or absent in 34 of 34 PV patients and also in 13 of 14 IMF patients. Impaired TPO-induced protein tyrosine phosphorylation in PV and IMF platelets was uniformly associated with markedly reduced or absent expression of Mpl. We conclude that reduced expression of Mpl is a phenotypic characteristic of platelets from patients with PV and IMF. The abnormality appears to distinguish PV from other forms of erythrocytosis and may be involved in the platelet function defect associated with PV.
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PMID:A novel thrombopoietin signaling defect in polycythemia vera platelets. 1101 90

Recently, a polymorphic base in exon 13 of the BCR gene (exon b2 of the major breakpoint cluster region) has been identified in the eighth position before the junctional region of BCR-ABL cDNA. Cytosine replaces thymidine; the corresponding triplets are AAT (T allele) and AAC (C allele), respectively, both coding for asparagine. Therefore, this polymorphism has no implication in the primary structure of BCR and BCR-ABL proteins. However, since the alteration is located close to the fusion region it may have a significant influence on the annealing of PCR primers, probes for real time PCR, and antisense oligonucleotides. We have developed a RT-PCR-based screening method to easily identify polymorphic BCR and BCR-ABL alleles in CML patients and normal individuals in order to estimate their frequency. After amplification from cDNA, a melting curve of a specific fluorogenic probe mapping to the 3' end of BCR exon b2 and spanning the polymorphism readily discriminates between normal and polymorphic BCR and BCR-ABL alleles. This reporter probe is 3' labeled with fluorescein and placed next to 5' LC Red640-labeled anchor probes mapping to the 5' ends of BCR exon b3 or ABL exon a2 so that resonance energy transfer occurs when the probes are hybridized (LightCycler technology). T and C alleles were discriminated by a melting temperature difference of the reporter probe of 3.2 K. We have investigated cDNAs derived from leukocytes from seven cell lines and a total of 229 individuals: normal donors, n = 15; BCR-ABL negative chronic myeloproliferative disorders, n=30; BCR-ABL negative acute leukemias, n= 11; b2a2BCR-ABL positive CML, n = 93; and b3a2BCR-ABL positive CML, n= 80. The frequency of the C allele was 33.0% in BCR-ABL negative individuals, 30.6% in b2a2BCR-ABL, and 23.8% in b3a2BCR-ABL positive CML. In CML patients, 27.7% of BCR-ABL and 27.2% of BCR alleles had the C allele (NS). In total, 132 of 458 (28.8%) exons b2 of BCR or BCR-ABL alleles demonstrated this polymorphism. We conclude that a thymidine/cytosine replacement occurs frequently in BCR exon b2. Probes for real time quantitative RT-PCR should be designed not to map to the critical region in order to avoid underestimation of the number of BCR-ABL transcripts.
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PMID:Frequent polymorphism in BCR exon b2 identified in BCR-ABL positive and negative individuals using fluorescent hybridization probes. 1106 38

Therapy-related changes of the bone marrow fiber content remain a controversial issue in hematopathology. This conflict of opinion firstly depends on difficulties to determine the quantity of fibers exactly (semiquantitative grading, morphometry, reference to cellularity). Secondly, the appropriate selection of patients with specific monotherapies including hydroxyurea (HU) and interferon-alpha (IFN) seems to present some problems. Finally, assessment of myelofibrosis is further biased by the different endpoints of sequential examinations. The latter shortcoming can be improved upon by the calculation of the myelofibrosis progression/regression index which describes the ratio between difference of fiber density and observation time. Using strictly defined therapeutic regimens and intervals between sequential trephine biopsies a stimulating effect of IFN administration on bone marrow fibrosis in Ph1+-chronic myelogenous leukemia (CML) has been found. This result is comparable with the failure of this agent to improve myelofibrosis (and splenomegaly) in a considerable number of patients with allied subtypes of chronic myeloproliferative disorders. This is in contrast to the effect HU exerts which is a more fibrolytic or even stabilizing influence on bone marrow fibrosis. This phenomenon is readily demonstrable by the assessment of dynamic features (myelofibrosis progression index). In addition, patients showing a rapid progression of myelofibrosis during IFN and HU treatment of Ph1+-CML are generally associated with a poor risk outcome and a significant worsening of survival.
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PMID:Comparative effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukemia. 1169 40

Except for chronic myelogenous leukemia (CML), chronic myeloproliferative disorders (CMPDs) include as main subtypes polycythemia vera (PV), chronic idiopathic myelofibrosis (IMF), and essential thrombocythemia (ET). A common finding in CMPDs is a clonal evolution associated with a significantly variable course, which may be complicated by thrombocythemia, (secondary) myelofibrosis, and finally acceleration (unstable phase) that merges into blastic crisis. New therapeutic modalities (chemo- and interferon therapy, bone marrow and stem cell transplantation) which were developed in the last decade and the striking differences in survival amongst the different subtypes warrant not only an unequivocal distinction from reactive and allied disorders, but a clear-cut classification as well. For this reason, a synoptical approach is essential including clinical data and, as a major diagnostic tool, a bone marrow biopsy. This concept finds expression in the new WHO classification, which also includes as rare subtypes chronic neutrophilic leukemia, eosinophilic leukemia, chronic hypereosinophilic syndrome, and finally unclassifiable entities. Histopathology of bone marrow biopsies reveals specific findings, in particular concerning megakaryopoiesis, which are characteristic for the different subtypes. These features facilitate the still controversially discussed differentiation of thrombocythemia that is frequently present, as is the case in initial (prefibrotic) IMF from ET. Moreover, in addition to clinical findings,the associated heterogeneity of bone marrow morphology indicates a stepwise evolution of the disease process and thus exerts a significant impact on survival, i.e., in CML regarding erythropoiesis and myelofibrosis and in IMF extent of myeloid metaplasia.
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PMID:[Chronic myeloproliferative disorders. The new WHO classification]. 1176 43

Contrasting the wealth of information that is available about various biological and therapeutic aspects of human CD34+ stem cells, little data exist concerning their quantity and dynamics as well as their mutual relationships with other hematopoietic constituents in the bone marrow of patients with chronic myeloproliferative disorders. In comparison with a control group frequency of progenitors is significantly increased in chronic myeloid leukemia (CML). Following different therapeutic modalities their quantity reflects therapeutic efficacy (responder and non-responder patients) and therefore exerts a predictive value regarding acceleration and blastic crisis. The significant correlations between fiber content and number of these precursors elucidates the complex interactions between stroma and progenitor cell differentiation and maturation. Following allogeneic bone marrow transplantation there is a rapid recovery of the CD34+ stem cell population in the first month. A higher number of these cells is related with graft size, an earlier independence for platelet transfusion and a more extended regeneration of erythro- and megakaryopoiesis. The slight increase in reticulin fibers in these patients may be associated with the complex and so far ill-defined pathomechanism of homing (adherence to the fibrous matrix). In idiopathic myelofibrosis (IMF) an increased number of CD34+ stem cells is found predominantly in the early (prefibrotic or mild fibrotic) hypercellular stages and probably indicates a higher proliferative activity of the precursor cell pool. According to sequential biopsies most patients with early IMF that later evolved into an overt fibrosclerotic stage usually display a reduction of progenitor cells during the development of myelofibrosis. The unequal distribution of CD34+ stem cells in the bone marrow versus spleen in IMF (advanced fibrosclerotic stage) is in support of the currently discussed hypothesis of splenic filtration and concentration of precursor cells as an essential feature of myeloid metaplasia. Regarding prognosis in CML a higher amount of CD34+ stem cells is significantly associated with an unfavorable survival and thus confirms the assumed implication of an accelerated phase of disease at onset. On the other hand, in polycythemia vera (PV) and IMF a low number of progenitors is probably due to a decreased proliferation rate (reduced hematopoietic turnover index) and therefore reflects a reduction in the regenerative capacity of hematopoiesis. For this reason, a presumptive defect in the recovery of normal and clonally transformed stem cells is speculated to add to the worsening of prognosis by causing the well-known bone marrow insufficiency in terminal stage PV and IMF.
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PMID:CD34+ stem cells in chronic myeloproliferative disorders. 1196 56

With the exception of chronic myeloid leukemia (CML), chronic myeloproliferative disorders (CMPDs) are a heterogeneous spectrum of conditions for which the molecular pathogenesis is not well understood. Most cases have a normal or aneuploid karyotype, but a minority present with a reciprocal translocation that disrupts specific tyrosine kinase genes, most commonly PDGFRB or FGFR1. These translocations result in the production of constitutively active tyrosine kinase fusion proteins that deregulate hemopoiesis in a manner analogous to BCR-ABL. With the advent of targeted signal transduction therapy, an accurate clinical and molecular diagnosis of CMPDs has become increasingly important. Currently, patients with PDGFRB or ABL fusion genes are candidates for treatment with Imatinib (STI571), but it is likely that alternative strategies will be necessary for the treatment of most other patients.
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PMID:Tyrosine kinase fusion genes in chronic myeloproliferative diseases. 1209 44

The chronic myeloproliferative disorders are clonal hematopoietic stem cell disorders and include chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and agnogenic myeloid metaplasia (AMM). These diseases are characterized by clonal expansion of the myeloid compartment, increased marrow angiogenesis, and varying risks for blastic transformation. A clear molecular abnormality exists (t(9;22) leading to the fusion of BCR-Abl) only for CML, which led to effective targeted therapy (STI-571). Since no similar pathogenetic mechanism has been discovered for the t(9;22) negative chronic myeloproliferative disorders, their respective diagnosis is currently based on a variety of rather cumbersome diagnostic criteria. Polycythemia vera is distinguished from reactive erythrocytosis through erythropoietin independent growth of erythroid progenitors in vitro, suppressed levels of endogenous erythropoietin, possible overexpression of PRV-1 (polycythemia rubra vera-1), decreased c-Mpl expression on megakaryocytes, as well as overexpression of bcl-xL, and potentially aberrant activity of the Jak-Stat pathway. ET is defined by thrombocytosis and is distinguished from reactive states by decreased megakaryocyte c-Mpl expression, and a propensity for thrombosis. AMM has been associated with a variety of observations including increased concentrations of pro-fibrotic cytokines, increased angiogenesis, and myeloid expansion. AMM is often indistinguishable clinically and prognostically from the advanced phases of other CMPD (specifically post-polycythemic and post-thrombocythemia myeloid metaplasia), all of which are subentities of a diagnosis of myelofibrosis with myeloid metaplasia (MMM). The management of CMPD patients is quite varied given the broad range of disease severity and survival observed. The role of stem cell transplantation is limited by the age and comorbidities encountered in CMPD patients. Since no broadly applicable therapy effects the mortality of the CMPD, management currently focuses on the prevention/palliation of disease morbidity (i.e. vascular complications, pruritus, organomegaly, constitutional symptoms). Palliative strategies which currently focus on non-specific myelosuppresion, will hopefully be soon replaced by targeted therapies as insight into pathogenetic mechanisms of these diseases evolves.
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PMID:Clinical and scientific advances in the Philadelphia-chromosome negative chronic myeloproliferative disorders. 1243 Sep 25

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