Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present research was to verify the prognostic value of some histologic bone marrow parameters in chronic myeloproliferative disorders. Diagnostic bone marrow biopsies were revised in 38 patients with chronic myeloid leukaemia, 30 with polycythemia vera, 14 with essential thrombocythemia and 16 with idiopathic myelofibrosis-myeloid metaplasia. An unfavourable clinical evolution was associated to "granulocytic" histotype in chronic myeloid leukaemia, to "erythrocytic/granulocytic and/or megacaryocytic" histotype in polycythemia vera, to "cluster" distribution of megacaryocytes in essential thrombocythemia, to classical myelofibrosis without osteomyelosclerosis in myelofibrosis-myeloid metaplasia. Bone marrow biopsy in chronic myeloproliferative disorders provides independent diagnostic and prognostic data; we support its routine execution in this group of hematologic malignancies.
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PMID:[Prognostic value of bone marrow biopsy in chronic myeloproliferative disorders]. 1286 37

Diagnosis of chronic myeloid leukemia and acute lymphoblastic leukemia requires the investigation of the Philadelphia chromosome translocation t(9;22) or the molecular detection of BCR-ABL fusion transcripts. Determination of the type of fusion transcript is crucial for quantitative molecular monitoring the course of the disease during treatment. Histopathologists, who usually use formalin-fixed tissues, may be confronted with the need to investigate the BCR-ABL rearrangement when evaluating tumor forming infiltrates and bone marrow trephines from patients presenting with chronic myeloproliferative disorders. Therefore, we have established a one-tube multiplex RT-PCR for the detection of common BCR-ABL fusion transcripts (b2a2, b3a2, e1a2) in routinely processed tissues and bone marrow trephines with respect to the inevitable fragmentation of ribonucleic acids in these specimens. RT-PCR products allow distinct and unequivocal differentiation of the underlying fusion in either the Major- or minor-breakpoint cluster region. Detection of BCR-ABL fusion transcripts by multiplex RT-PCR in routinely processed and fixed tissues is a time- and cost-sparing tool for definite diagnosis of typical chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia.
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PMID:Multiplex RT-PCR for the detection of common BCR-ABL fusion transcripts in paraffin-embedded tissues from patients with chronic myeloid leukemia and acute lymphoblastic leukemia. 1296 Jun 92

The classification of myeloid neoplasms now includes CMPD, mixed CMPD/ MDS, MDS, and acute myeloid leukemias. CMPD and CMPD/MDS, both clonal stem cell diseases, share myeloproliferative features, including typical hypercellular marrows, organomegaly, and cell lineage maturation. The CMPD generally differ by which myeloid cell lineage dominates hematopoiesis, and the main diseases include CML, PV, ET, and CIM. The mixed CMPD/MDS disorders also show dysplastic features and variable amounts of effective hematopoiesis; these disorders include CMML, JMML, and atypical CML. Given the overlap in morphology among these diseases, correlation with clinical, hematologic, and cytogenetic/molecular genetic findings is imperative for precise classification.
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PMID:Pathology of the myeloproliferative diseases. 1456 Jul 77

The development of various kinds of autoimmune disease as a result of interferon-alpha (IFN-alpha) therapy has been reported among chronic myeloproliferative disorders(CMPD) including chronic myeloid leukemia(CML). Therefore, we investigated the frequency of autoimmune disorders in 33 patients with hematopoietic diseases treated with IFN-alpha in our department. Thirty-three patients (12 females, 21 males) included cases of CML (n = 23), essential thrombocythemia (ET) (n = 1), multiple myeloma (n = 8), and hypereosinophilic syndrome (HES) (n = 1). Autoantibodies (ANA, dsDNA, and RAPA), thyroid grand functions, and coagulant functions were examined. Twenty-five out of 33 patients were treated with natural IFN-alpha, and 8 patients were treated with recombinant IFN-alpha 2b (rIFN alpha-2b). Three patients were treated with IFN and anticancer agents. Antinuclear antibodies were detected in 2 of 33 patients. RAPA and anti-thyroglobulin antibody became positive in 3 and 4 patients, respectively. Ten patients showed low serum levels of either free T3 and/or free T4. However, none of them showed any clinical symptoms for developing autoimmune diseases. In addition, circulating anticoagulant antibodies were detected in 3 of 23 patients with CML treated with rIFN alpha-2b, but in no cases treated with natural IFN-alpha. Although none of the patients developed autoimmune diseases, we concluded that patients receiving IFN therapy should be carefully monitored for clinical signs and symptoms of autoimmune disorders.
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PMID:[Autoimmune phenomena during interferon-alpha therapy for hematopoietic disorders]. 1465 Sep 58

Essential thrombocytosis is one of the chronic myeloproliferative disorders that includes polycythemia vera, chronic myelogenous leukemia, and agnogenic myeloid metaplasia. Despite established diagnostic criteria and greater than a quarter century of study, there are still several diagnostic and management dilemmas that plague researchers and clinicians alike. We present a case of essential thrombocytosis in a patient with multiple sequelae.
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PMID:Essential thrombocytosis: diagnostic and treatment dilemmas. 1475 Jul 50

Angiogenesis is critical for the clinical progression of haematopoietic malignancies and depends on angiogenic factors. Angiogenin is a powerful factor produced by neoplastic cells and host microenvironment. High levels of soluble angiogenin (sAng) correlate with a poor prognosis in patients affected by acute myeloid leukaemia and myelodysplastic syndromes, but no data are available on sAng in chronic myeloproliferative disorders (CMD). Therefore, in this study we investigated the clinical significance of the angiogenin in sera of patients with chronic myeloid leukaemia (CML) (n = 14) or essential thrombocythaemia (ET) (n = 20), and correlated them with those of soluble transforming growth factor-beta(1) (sTGF beta(1)). Enzyme-linked immunosorbent assay detected (P < 0.05) higher levels of sAng in CMD compared with healthy subjects (1026.74 +/- 464.60 pg/mL and 196.00 +/- 39.90 pg/mL, respectively). The highest levels of sAng were detected in CML patients (1349.23 +/- 549.55 pg/mL). Interestingly, CML patients who achieved haematological remission after interferon therapy showed circulating levels of angiogenin significantly (P < 0.05) decreased when compared with those at diagnosis. In ET patients, levels of angiogenin (889.34 +/- 267.66 pg/mL) and sTGF beta(1) (76.69 +/-6.08 pg/mL) were higher (P < 0.05) compared with healthy controls (57.93 +/- 19.39 pg/mL). No correlation was found between levels of sAng and levels of sTGF beta(1) or platelet count among ET patients. Our results show for the first time that elevated blood levels of angiogenin feature chronic myeloid malignancies, suggesting a role of angiogenin in the pathogenesis of these diseases.
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PMID:Levels of soluble angiogenin in chronic myeloid malignancies: clinical implications. 1512 20

Imatinib mesylate is a small molecule drug that in vitro inhibits the Abelson (Abl), Arg (abl-related gene), stem cell factor receptor (Kit), and platelet-derived growth factor receptor A and B (PDGFRA and PDGFRB) tyrosine kinases. The drug has acquired therapeutic relevance because of similar inhibitory activity against certain activating mutations of these molecular targets. The archetypical disease in this regard is chronic myeloid leukemia, where abl is constitutively activated by fusion with the bcr gene (bcr/abl). Similarly, the drug has now been shown to display equally impressive therapeutic activity in eosinophilia-associated chronic myeloproliferative disorders that are characterized by activating mutations of either the PDGFRB or the PDGFRA gene. The former usually results from translocations involving chromosome 5q31-33, and the latter usually results from an interstitial deletion involving chromosome 4q12 (FIP1L1-PDGFRA). In contrast, imatinib is ineffective, in vitro and in vivo, against the mastocytosis-associated c-kit D816V mutation. However, wild-type and other c-kit mutations might be vulnerable to the drug, as has been the case in gastrointestinal stomal cell tumors. Imatinib is considered investigational for the treatment of hematologic malignancies without a defined molecular drug target, such as polycythemia vera, myelofibrosis with myeloid metaplasia, and acute myeloid leukemia.
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PMID:Imatinib targets other than bcr/abl and their clinical relevance in myeloid disorders. 1516 33

The chronic myeloproliferative disorders (MPD), polycythemia vera (PV), chronic idiopathic myelofibrosis (IMF), essential thrombocytosis (ET), and chronic myelogenous leukemia (CML), are thought to be clonal disorders arising in a multipotent hematopoietic progenitor cell. However, establishing the diagnosis of an MPD other than CML is problematic due to a lack of clinically applicable clonal markers. Furthermore, in some patients, in whom a classical MPD phenotype is present, the hematopoietic stem cells appear to be polyclonal, suggesting that the chronic MPD other than CML may actually be a genetically heterogeneous group of disorders. Furthermore, since the aberrant clone is believed to arise from a multipotent hematopoietic stem cell, the non-CML chronic MPD-ET, PV, and IMF-could be related. Additional unresolved issues regarding the MPD include: identification of the multipotent hematopoietic progenitor cell involved, the molecular basis for the clinical heterogeneity amongst the individual MPD, the clinical significance of clonality in non-CML MPD, and reconciliation of therapy with the clonal and clinical heterogeneity of these disorders. Determination of clonality has largely been carried out using X chromosome-linked polymorphisms, but such studies are limited to women and with increasing patient age are compromised by skewing of allelic expression in both neutrophils and T lymphocytes, making the results difficult to interpret. X chromosome-linked polymorphism studies have indicated that in PV the target stem cell is one that gives rise to both lymphoid and myeloid progenitors. Recently, two epigenetic markers have been identified in the MPD: impaired expression of the thrombopoietin receptor, Mpl, in platelets and megakaryocytes, and overexpression in neutrophils of the mRNA of a gene designated polycythemia rubra vera-1 (PRV-1). The role of these epigenetic abnormalities in the diagnosis of the MPD remains to be established. Currently, given the unresolved issues with respect to the clinical and clonal heterogeneity of the MPD, treatment needs to be tailored individually in patients with an MPD.
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PMID:The chronic myeloproliferative disorders: clonality and clinical heterogeneity. 1519 May 15

A total of 106 trephine biopsy specimens with clinical, laboratory and pathology findings corresponding to chronic myeloproliferative disorders (CMPD) were analyzed to reveal the nature of the lymphoid infiltrate in the bone marrow. Histological investigation in 31 chronic myeloid leukemia (CML), 29 CMPDs not otherwise specified (CMPD-NOS), 28 essential thrombocytosis (ET), 15 polycythemia vera (PV) and three chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) exhibited in 32% various amounts of lymphocytic infiltrate of sparsely to moderately diffuse or nodular types in the bone marrow, but the reactive or coinciding lymphomatous nature could not be revealed by histology alone in the majority of cases. PCR analysis of the immunoglobulin heavy chain (IgH) gene rearrangement was successfully performed in 81 out of the 106 DNA specimens extracted from formol-paraffin blocks. Out of the 81 samples with good-quality DNA, 18 gave a single or double discrete amplification band(s), which was reproducible only in four specimens. Sequencing finally proved monoclonal B-cell population of both pre- and postfollicular origin in all four samples (5%), one CML and three CMPD-NOS. Detailed clinical and pathological investigations indicated overt B-cell malignant lymphoma with clonal relationship to the CMPD in two out of these four patients. We conclude that detailed molecular analysis of IgH gene rearrangement in bone marrow samples of CMPD patients is needed to identify the true monoclonal B-cell infiltration, which-even without overt malignant lymphoma-may occur in this group of disorders. Modern Pathology (2004) 17, 1521-1530, advance online publication, 16 July 2004; doi:10.1038/modpathol.3800225.
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PMID:Increased incidence of monoclonal B-cell infiltrate in chronic myeloproliferative disorders. 1525 12

Basic fibroblast growth factor (bFGF) is an important growth factor involved in clonal hematopoietic expansion, neoangiogenesis, and bone marrow fibrosis, all of which are important pathobiologic features of clonal chronic myeloproliferative disorders (CMPD) and myelodysplastic syndromes (MDS). The aim of this study was to assess circulating bFGF concentrations in patients with CMPD and MDS with respect to the presence of bone marrow fibrosis in histopathologic examination. The study group comprised 18 patients with CMPD (six female, 12 male; median age 50 years), seven patients with MDS (one female, six male; median age 66 years) and 10 healthy adults as controls (four female, six male; median age 29 years). CMPD group included six chronic myelogenous leukemia (CML), seven essential thrombocythemia (ET), three polycythemia vera (PV), two agnogenic myeloid metaplasia (AMM). All seven MDS patients were the FAB subtype of refractory anemia (RA). Bone marrow biopsy sections stained with hematoxylin and eosin (H & E) and for reticulin were examined for the presence of fibrosis. The median plasma bFGF level was 18.2 pg/ml (interquartile range, IQR: 15.2-26.7) in patients with CMPD, 18.0 pg/ml (IQR: 15.8-26.4) in patients with MDS, 13.6 pg/ml (IQR: 9.9-20.0) in the control group. The bFGF levels were significantly higher in patients with CMPD in comparison with the healthy control group (P = 0.031). Circulating bFGF tended to be significantly lower in relation to the development of marrow fibrosis (P = 0.028). The complicated interactions of bFGF and fibrosis in the context of CMPD may be either 'cause' or 'effect'. The bFGF might represent an important link between angiogenesis, fibrosis, and clonal neoplastic hematopoiesis during the development of CMPD.
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PMID:Plasma basic fibroblast growth factor and bone marrow fibrosis in clonal myeloproliferative disorders. 1527 63


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