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

Chronic myeloproliferative disorders are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid cell lineages in the bone marrow. The WHO classification describes six major groups of chronic myeloproliferative disorders, as follows: chronic myeloid leukemia, chronic neutrophilic leukemia, chronic eosinophilic leukemia, polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis. The diagnosis of chronic myeloid leukemia and certain types of chronic eosinophilic leukemia are based on the detection of fusion genes (in chronic myeloid leukemia the BCR/ABL fusion gene, and in chronic eosinophilic leukemia the FIP1L1-PDGFRalpha gene). On the other hand molecular markers for polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis were lacking, making it difficult to identify these disorders clearly. The authors investigated the incidence of the newly identified somatic point mutation V617F of the Janus-2 tyrosine kinase in patients with polycythemia vera, essential thrombocythemia and myelofibrosis. Janus-2 kinase is a cytoplasmic, non-receptor protein-tyrosine kinase with a key role in signal transduction from multiple hematopoietic growth factor receptors. The mutant protein is constitutively phosphorylated and is able to activate its downstream signaling pathways in the absence of any cytokine, thereby contributing to the pathogenesis of chronic myeloproliferative disorders. The authors investigated DNA samples from 132 patients with chronic myeloproliferative disorders. The V617F mutation was detected by allele-specific polymerase chain reaction, and the patients were genotyped by a DNA tetra-primer amplification refractory mutation system assay. Approximately 73% of polycythemia vera, 60% of essential thrombocythemia and 67% of myelofibrosis showed the JAK2 V617F mutation. Using the amplification refractory mutation system assay, the frequency of homozygotes was 17.5% in polycythemia vera, 5.4% in essential thrombocythemia and 0% in myelofibrosis. The authors established an effective polymerase chain reaction based method for the identification of JAK2 mutation in the routine oncohematologic diagnostics.
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PMID:[Novel method in diagnosis of chronic myeloproliferative disorders--detection of JAK2 mutation]. 1740 11

The aim of study was to investigate the importance of chromosome aberration in differential diagnosis of eosinophilia and the chromosomal aberrations involved in patients with clonal eosinophilia. 65 cases of eosinophilia were collected and chromosome specimens of bone marrow cells were prepared by 24-hour culture, and G-banding technique was used for karyotyping. The results showed that out of 65 cases, chromosome 16 inversion was detected in 9 patients suspected as M(4Eo), and among the other 56 cases, 5 were detected with chromosomal aberrations (8.9%). Combining clinical, hematological and cytogenetical data, the 5 patients were diagnosed as acute myeloid leukemia with eosinophilia, chronic eosinophilic leukemia, 8p11 myeloproliferative syndrome, chronic myeloid leukemia in acute phase and acute myeloid leukemia-M(4Eo) respectively. The detected chromosomal aberrations were +14, t (5; 12) (q31; p13), t (8; 9) (p11; q32), t (9; 22) (q34; q11) and inv (16) (p13 q22). In conclusion, cytogenetical detection is very important in differential diagnosis of clonal eosinophilic disorders and chronic eosinophilic leukemia, which is suggested to be done routinely in clinic.
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PMID:[Cytogenetic study on eosinophilia]. 1760 43

The 2001 World Health Organization (WHO) treatise on the classification of hematopoietic tumors lists chronic myeloproliferative diseases (CMPDs) as a subdivision of myeloid neoplasms that includes the four classic myeloproliferative disorders (MPDs)-chronic myelogenous leukemia, polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF)-as well as chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) and 'CMPD, unclassifiable'. In the upcoming 4th edition of the WHO document, due out in 2008, the term 'CMPDs' is replaced by 'myeloproliferative neoplasms (MPNs)', and the MPN category now includes mast cell disease (MCD), in addition to the other subcategories mentioned above. At the same time, however, myeloid neoplasms with molecularly characterized clonal eosinophilia, previously classified under CEL/HES, are now removed from the MPN section and assembled into a new category of their own. The WHO diagnostic criteria for both the classic BCR-ABL-negative MPDs (that is PV, ET and PMF) and CEL/HES have also been revised, in the 2008 edition, by incorporating new information on their molecular pathogenesis. The current review highlights these changes and also provides diagnostic algorithms that are tailored to routine clinical practice.
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PMID:Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. 1841 5

Vascular endothelial growth factor (VEGF) is produced in neoplastic cells in various myeloid neoplasms and may act as an autocrine growth-regulator. We have examined the expression of five VEGF receptors (VEGR1/Flt-1, VEGFR2/KDR, Flt-4, neuropilin-1 = NRP-1, NRP-2) in leukemic cells obtained from patients with acute myeloid leukemia (n = 28), chronic myeloid leukemia (n = 14), chronic eosinophilic leukemia (n = 3), chronic myelomonocytic leukemia (n = 9), or mast cell leukemia/systemic mastocytosis (n = 3) as well as in respective cell lines. Expression of VEGFR mRNA was analyzed by RT-PCR, and expression of VEGFR protein by immunocytochemistry. In most patients, leukemic cells expressed NRP-1 mRNA and NRP-2 mRNA independent of the type of disease. By contrast, transcripts for Flt-1, KDR, and Flt-4 were expressed variably without a clear correlation to the type of leukemia. Expression of VEGF receptors was also demonstrable at the protein level in all cases tested. In conclusion, neoplastic cells in myeloid leukemias frequently express VEGFR including NRP-1 and NRP-2.
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PMID:Myeloid leukemias express a broad spectrum of VEGF receptors including neuropilin-1 (NRP-1) and NRP-2. 1791 67

Recent years showed significant progress in the molecular characterization of the chronic myeloproliferative disorders (CMPD) which are classified according to the WHO classification of 2001 as polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET), CMPD/unclassifiable (CMPD-U), chronic neutrophilic leukemia, and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome, all to be delineated from BCR/ABL-positive chronic myeloid leukemia (CML). After 2001, the detection of the high frequency of the JAK2V617F mutation in PV, CIMF, and ET, and of the FIP1L1-PDGFRA fusion gene in CEL further added important information in the diagnosis of CMPD. These findings also enhanced the importance of tyrosine kinase mutations in CMPD and paved the way to a more detailed classification and to an improved definition of prognosis using also novel minimal residual disease (MRD) markers. Simultaneously, the broadening of therapeutic strategies in the CMPD, e.g., due to reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation and the introduction of tyrosine kinase inhibitors in CML, in CEL, and in other ABL and PDGRFB rearrangements, increased the demands to diagnostics. Therefore, today, a multimodal diagnostic approach combining cytomorphology, cytogenetics, and individual molecular methods is needed in BCR/ABL-negative CMPD. A stringent diagnostic algorithm for characterization, choice of treatment, and monitoring of MRD will be proposed in this review.
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PMID:The diagnosis of BCR/ABL-negative chronic myeloproliferative diseases (CMPD): a comprehensive approach based on morphology, cytogenetics, and molecular markers. 1793 25

Myeloproliferative syndromes (MPS) are clonal proliferation of hematopoietic progenitor cells characterized by proliferation of 1 or a few cell lines such as granulocytic, erythroid, megakaryocytic or mastocytic. These syndromes include: chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic eosinophilic leukemia/hypereosinophilic syndrome, chronic neutrophilic leukemia and systemic mastocytosis. Diagnosis of MPS is often difficult due to need of differential diagnosis with reactive proliferation caused by primarily non-hematological factors. Differentiation of individual MPS forms is also difficult because of overlapping of particular clinical or laboratory adnormalities. Discovery of specific molecular aberrations in the last few years facilitates diagnostic procedures. The discovered gene mutations or their fusions are associated with production of proteins possessing tyrosine kinase properties. These discoveries resulted in the successful introduction of the targeted therapy with tyrosine kinase inhibitors in the recent years.
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PMID:Myeloproliferative syndromes: diagnosis and therapeutic options. 1920 55

Eosinophilia is a recurrent feature and diagnostic clue in several hematologic malignancies. In stem cell- and myelopoietic neoplasms, eosinophils are derived from the malignant clone, whereas in lymphoid neoplasms and reactive states, eosinophilia is usually triggered by eosinopoietic cytokines. Myeloid neoplasms typically presenting with eosinophilia include chronic myeloid leukemia, chronic eosinophilic leukemia (CEL), other myeloproliferative neoplasms, some acute leukemias, advanced mast cell disorders, and rare forms of myelodysplastic syndromes. Diagnostic evaluations in unexplained eosinophilia have to take these diagnoses into account. In such patients, a thorough hematologic work-up including bone marrow histology and immunohistochemistry, cytogenetics, molecular markers, and a complete staging of potentially affected organ systems has to be initiated. Endomyocardial fibrosis, the most dangerous cardiovascular complication of the hypereosinophilic state, is frequently detected in PDGFR-mutated neoplasms, specifically in FIP1L1/PDGFRA+ CEL, but is usually not seen in other myeloid neoplasms or reactive eosinophilia, even if eosinophilia is recorded for many years. Treatment of hypereosinophilic patients depends on the variant of disease, presence of end organ damage, molecular targets, and the overall situation in each case. In a group of patients, oncogenic tyrosine kinases (TK) such as FIP1L1/PDGFRA, can be employed as therapeutic targets by using imatinib or other TK-blocking agents.
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PMID:Pathogenesis, classification, and therapy of eosinophilia and eosinophil disorders. 1924 39

According to the 2008 World Health Organization classification system for hematologic malignancies, the myeloproliferative neoplasms (MPN) include chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, primary myelofibrosis, mastocytosis, chronic eosinophilic leukemia-not otherwise specified, chronic neutrophilic leukemia, and "MPN, unclassifiable." All of these clinicopathologic entities are characterized by stem cell-derived clonal myeloproliferation, and their phenotypic diversity is ascribed to the occurrence of distinct oncogenic events. In the last 4 years, new JAK2 and MPL mutations have been added to previously described ABL and KIT mutations as molecular markers of disease in MPN. These discoveries have markedly simplified the approach to clinical diagnosis and have also provided molecular targets for the development of small-molecule drugs. In the current article, the authors provide a clinically oriented overview of MPNs in terms of their molecular pathogenesis, classification, diagnosis, and management.
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PMID:Advances in understanding and management of myeloproliferative neoplasms. 1936 82

The first formal classification of chronic myeloid neoplasms is credited to William Dameshek, who in 1951 described the concept of "myeloproliferative disorders (MPD)" by grouping together chronic myelogenous leukemia, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2001 World Health Organization (WHO) classification of myeloid malignancies included these MPDs under the broader category of chronic myeloproliferative diseases (CMPD), which also included chronic neutrophilic leukemia, chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES), and "CMPD, unclassifiable." The revised 2008 WHO classification system featured the following changes: 1) the term "CMPD" was replaced by "myeloproliferative neoplasm (MPN)," 2) mast cell disease was formally included under the category of MPN, and 3) the subcategory of CEL/HES was reorganized into "CEL not otherwise specified (CEL-NOS)" and "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1"; CEL-NOS remained a subcategory of "MPN," whereas the latter neoplasms were now assigned a new category of their own. Furthermore, diagnostic criteria for PV, ET, and PMF were revised by incorporating recently described molecular markers (eg, JAK2 and MPL mutations) as well as underscoring the role of histology in differentiating reactive from clonal myeloproliferations. As a result, red cell mass measurement is no longer necessary for the diagnosis of PV, and ET can now be diagnosed at a lower platelet count threshold. The revised WHO document continues to promote the recognition of histologic categories as a necessary first step toward the genetic characterization of myeloid malignancies.
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PMID:The 2008 World Health Organization classification system for myeloproliferative neoplasms: order out of chaos. 1947 96

The chronic myeloproliferative disorders (MPDs) include the spectrum of clonal hematopoietic stem cell disorders whose phenotype derive from the primary cell expanded in a proliferative state. The MPDs (which include polycythemia vera (PV), essential thrombocythemia (ET), chronic eosinophilic leukemia (CEL), primary myelofibrosis (PMF), chronic myelomonocytic leukemia (CMML), and systemic mast cell disease (SMCD)) exclude chronic myeloid leukemia (CML) because of the pathognomic importance of the BCR-ABL translocation for the diagnosis and treatment of this disorder with imatinib mesylate. Empiric use of imatinib mesylate against the spectrum of BCR-ABL negative MPDs has had mixed results. Significant benefits were obtained when empiric use of imatinib in CEL and CMML led to significant clinical benefit and the discovery of the role of rearrangements of the platelet derived growth factor receptor -alpha (PDGFRa-FIP1L1 in CEL and SMCD) and -beta (PDGFRb through TEL-PDGFRb) for CMML). Empiric use of imatinib in PMF has been disappointing, and in PV quite modest. Although next generation Abelson kinase inhibitors such as dasatinib or nilotinib may expand the role for these agents in MPDs, targeted inhibition of the mutant kinase JAK2(V617F) is more likely to make significant therapeutic gains in the classic MPDs of PV, ET, and PMF.
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PMID:Imatinib and tyrosine kinase inhibition, in the management of BCR-ABL negative myeloproliferative disorders. 1970 23


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