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 Authors have studied bone marrow CFUc and CLFC of 8 cases affected by idiopathic myelofibrosis, 7 by chronic granulocytic leukemia, 6 by polycythemia, and 3 by sideroblastic anemia. The authors studied also C.S.F. activity in peripheral blood of 8 cases. The method of Pike and Robinson for in agar culture was utilized. The results indicated a correlation between increase of clusters/colonies fraction, growth of blasts-like clusters, reduction of C.S.F. activity in peripheral blood and transformation in acute leukemia of preleukemic syndromes.
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PMID:[Evaluation of the proliferative activity of hematopoietic cells in preleukemic syndromes]. 693 4

We report here two cases of a previously undescribed myeloproliferative disorder. Both were young adult males who presented with generalized lymphadenopathy, splenomegaly, leukocytosis, polycythemia, and persistent thrombocytopenia. The leukocyte alkaline phosphatase (LAP) score was low in both cases, and the bone marrow was hypercellular without dysplasia or fibrosis, but lacked the Philadelphia chromosome, BCR gene rearrangement, or other karyotypic abnormalities. The clinical course was indolent in each case. One patient died from an unusual "blast crisis" after 12 years, while the second patient remains in a complete hematologic remission on hydroxyurea and alpha interferon 4 years from diagnosis. Interestingly, changes in therapy in this patient have consistently resulted in precise and concerted fluctuations in his blood counts, with the red and white cells cycling together and the platelets and mean corpuscular volume (MCV) changing concomitantly but in the opposite direction. This unique myeloproliferative disorder is distinguishable from all previously described forms of chronic myeloid leukemia and other myeloproliferative syndromes.
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PMID:A new myeloproliferative syndrome. 786 27

Myeloproliferative diseases include primary polycythemia, primary thrombocytosis, primary myelofibrosis and chronic myeloid leukaemia. The average survival of patients with the former two diagnoses is more than 10 years, in the subsequent two it is only 5 years. Standard treatment of polycythemia still remains phlebotomy, only in patients with associated thrombocythemia and complications caused by it cytoreduction treatment is recommended (hydroxyurea, busulphan or interferon alpha). Patients with primary thrombocythemia due to hypofunctional thrombocytes suffer frequently from haemorrhagic and thrombotic complications. The objective of treatment is therefore to achieve a normal number of thrombocytes. Medicamentous procedures are the same as in primary polycythemia. In primary myelofibrosis and chronic myeloid leukaemia it is also necessary to reduce the pathological population in bone marrow by the above mentioned therapeutic procedures. Contrary to the former two diagnoses, the survival of patients with primary myelofibrosis is shorter and the patients need more supportive treatment. In chronic myeloid leukaemia also transplantation treatment can be used, if a suitable donor is available. The decision between classical and transplantation treatment must be made soon after establishment of the diagnosis. The objective of the following paper is to inform readers on the clinical course of different diseases, on differential diagnostic problems and changes in therapeutic procedure which have developed in recent years.
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PMID:[Myeloproliferative diseases]. 897 64

Myeloproliferative disorders (MPD) are prone to modification and evolution during the progression of the disease. While post-polycythemia myeloid metaplasia and chronic myelogenous leukemia following polycythemia vera have been frequently described, no report is available about the evolution of polycythemia vera into essential thrombocythemia. Our case is probably the first report on this occurrence. In the course of a fortuitous observation of electrocardiographic alterations, a diagnosis of polycythemia vera was ruled out in accordance with polycythemia vera study group criteria. At the time of diagnosis, RBC was 6 x 10(12)/L, WBC 15 x 10(9)/L, Ht 59% and platelets 1000 x 10(9)/L. The patient was treated with phlebotomies and radioactive phosphorus achieving a good remission or the disease. Five years later, platelets rose to over 3300 x 10(9)/L without significant modification or RBC, WBC and Ht. The restaging or the disease was consistent for an essential thrombocythemia. In particular, RBC mass was within normal levels. During the last ten years, the patient has been followed recurrently and the blood picture remained stationary, without an increase in the hematocrit but with a platelet count between 658 and 800 x 10(9)/L. We conclude that this report may complete data concerning the evolution of MPD in others.
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PMID:Essential thrombocythemia following polycythemia vera: an unusual sequence. 915 Dec 4

Chronic myeloproliferative disorders (CMPD) are neoplastic disorders of the hematopoietic stem cell. Four different entities are defined: chronic myeloid leukemia (CML), polycythemia vers, essential thrombocythaemia, and idiopathic myelofibrosis. In addition, overlapping entities within the CMPDs and between CMPDs and myelodysplastic syndrome have been described. Diagnostic measures are performed to classify the subtype exactly and to assess risk factors and prognosis. Cytogenetic and molecular analyses are mandatory for the characterization of the malignant clone. Hydroxyurea and interferon-alpha have proven effective in all CMPE. In CML, specific inhibition of the elevated ABL tyrosine kinase activity with imatinib is associated with high response rates. Allogeneic stem cell transplantation is the only curative treatment option for all entities. In CML, the decision-making analysis should be based on established scores. In BCR-ABL negative CMPDs an allogeneic stem cell transplantation should only be performed in patients with unfavorable prognosis.
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PMID:[Chronic myeloproliferative diseases. Diagnosis and therapy]. 1467 16

We report phase II trial results of the use of oral anagrelide hydrochloride for treating 38 patients with hydroxyurea (HU)-resistant thrombocytosis accompanying chronic myeloid leukemia (CML). Anagrelide's efficacy was well established during a phase II study of more than 400 patients with one of the four myeloproliferative disorders: essential thrombocythemia, polycythemia, idiopathic myelofibrosis, and CML. In the last subgroup, there were 114 CML patients with significant thrombocytosis treated with anagrelide. Out of these patients, 38 had symptoms of thrombosis or hemorrhage and had thrombocytosis resistant to HU. They were then treated with anagrelide at an initial dose of 2.0 mg/day, followed by modifications based upon response and toxicity. In all, 71% of these patients responded with platelet reductions of more than 50% in a median time of approximately 4 weeks. The response rate was not influenced by age, gender, or prior thrombosis or hemorrhage. Importantly, the response rate to anagrelide in patients refractory to prior HU was essentially the same as that of the other 76 CML patients. Treatment with anagrelide was well tolerated and without undue toxicity. Reduction of excessive platelet counts by anagrelide sometimes occurring in CML may lead to the prevention of thrombohemorrhagic complications occurring in this clinical setting and is relevant even in those patients in whom imatinib mesylate is primary therapy.
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PMID:Anagrelide is effective in treating patients with hydroxyurea-resistant thrombocytosis in patients with chronic myeloid leukemia. 1551 Feb 7

By definition, myeloproliferative disorders (MPDs) are caused by an acquired somatic mutation of a hematopoietic progenitor/stem cell and have sporadic occurrence. However, well-documented families exist with first-degree relatives acquiring one or several MPDs. It is reasonable to assume that the germ-line mutation(s) or genetic background must facilitate or predispose for one or several somatic mutation(s) that lead to the MPD that is indistinguishable from the sporadic form. This is best documented in familial polycythemia vera (PV), which appears to be inherited as an autosomal dominant disorder with incomplete penetrance. However, there are also families wherein members develop any combination of MPDs, including PV, essential thrombocythemia (ET), chronic myelocytic leukemia (CML), and idiopathic myelofibrosis (IMF). A separate group of familial diseases is the familial thrombocythemias, wherein germ-line mutations in the genes for thrombopoietin or its receptor, MPL, cause polyclonal hereditary thrombocythemia, which may be clinically indistinguishable from ET. Patients with the congenital polycythemic condition "primary familial and congenital polycythemia" (PFCP) have characteristically decreased erythropoietin (Epo) levels similar to PV, hypersensitive erythroid progenitors, and low Epo levels; as such, this condition is often confused with PV. Therefore, PFCP will also be discussed here, while other congenital polycythemic states such as the Chuvash polycythemia that have elevated or inappropriately normal Epo levels will be omitted from this review in view of their distinct phenotype and unique laboratory features.
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PMID:Lessons from familial myeloproliferative disorders. 1621 40

Myeloproliferative disorders (MPDs) are heterogeneous diseases that occur at the level of a multipotent hematopoietic stem cell. They are characterized by increased blood cell production related to cytokine hypersensitivity and virtually normal cell maturation. The molecular pathogenesis of the MPDs has been poorly understood, except for chronic myeloid leukemia (CML), where the Bcr-Abl fusion protein exhibits constitutive kinase activity. Since some rare MPDs are also related to a dysregulated kinase activity, a similar mechanism was thought to be likely responsible for the more frequent MPDs. We investigated the mechanisms of endogenous erythroid colony formation (EEC) by polycythemia vera (PV) erythroid progenitor cells and found that EEC formation was abolished by a pharmacological inhibitor of JAK2 as well as an siRNA against JAK2. JAK2 sequencing revealed a unique mutation in the JH2 domain leading to a V617F substitution in more than 80% of the PV samples. This mutation in the pseudokinase autoinhibitory domain results in constitutive kinase activity and induces cytokine hypersensitivity or independence of factor-dependent cell lines. Retroviral transduction of the mutant JAK2 into murine HSC leads to the development of an MPD with polycythemia. The same mutation was found in about 50% of patients with idiopathic myelofibrosis (IMF) and 30% of patients with essential thrombocythemia (ET). Using different approaches, four other teams have obtained similar results. The identification of the JAK2 mutation represents a major advance in our understanding of the molecular pathogenesis of MPDs that will likely permit a new classification of these diseases and the development of novel therapeutic approaches.
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PMID:A unique activating mutation in JAK2 (V617F) is at the origin of polycythemia vera and allows a new classification of myeloproliferative diseases. 1630 80

JAK2V617F, a somatic gain-of-function mutation involving the JAK2 tyrosine kinase gene, occurs in nearly all patients with polycythemia vera (PV) but also in a variable proportion of patients with other myeloid disorders; mutational frequency is estimated at approximately 50% in both essential thrombocythemia (ET) and myelofibrosis (MF), up to 20% in certain subcategories of atypical myeloproliferative disorder (atypical MPD), less than 3% in de novo myelodysplastic syndrome (MDS) or acute myeloid leukemia, and 0% in chronic myeloid leukemia (CML). Accordingly, there is now molecular justification for grouping PV, ET, and MF together in a distinct MPD category (i.e., classic, BCR-ABL(-) MPD) that is separate from chronic myeloid leukemia (CML), MDS, and atypical MPD. To date, JAK2V617F has not been described in patients with reactive myeloproliferation, lymphoid disorders, or solid tumor. Therefore, the presence of JAK2V617F strongly suggests an underlying MPD and it is therefore reasonable to consider JAK2V617F-based laboratory tests for the evaluation of polycythemia, primary thrombocytosis, unexplained leukocytosis, bone marrow fibrosis, or abdominal vein thrombosis. Current information on disease-specific prognostic relevance of JAK2V617F is inconclusive and confounded by inter-study differences in the performance of mutation screening assays. Regardless, the discovery of JAK2V617F has reinforced the pathogenetic contribution of JAK-STAT signaling in MPD and identifies JAK2 as a valid drug target.
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PMID:Classification, diagnosis and management of myeloproliferative disorders in the JAK2V617F era. 1712 67

The determination of leukocyte alkaline phosphatase (LAP) is used as an aid to diagnose many diseases in the laboratory. For example, it can be used to distinguish chronic myeloid leukemia (CML) from other myeloproliferative disorders (particularly myelofibrosis and polycythemia) and leukemoid reactions (LR). Traditionally, this test is performed with the use of subjective cytochemical assays that assign a score to the level of LAP. Here we present a nonsubjective, quantitative, sensitive, and inexpensive chemiluminescent technique that determines LAP based on the commercial reagent Immulite (AMPPD). To validate this methodology, intact leukocytes obtained from 32 healthy subjects, nine CML patients, and nine LR patients were submitted to the optimized protocol. By measuring the light emission elicited by four concentrations of neutrophils, we were able to estimate the activity of LAP per cell (the slope of the curve obtained by linear regression). A high linear correlation was found between the chemiluminescent result (slope) and the cytochemical score. The slope for healthy individuals ranged between 0.61 and 8.49 (10(-5) mV.s/cell), with a median of 2.04 (10(-5) mV.s/cell). These results were statistically different from those of CML patients (range=0.07-1.75, median=0.79) and LR patients (range= 3.84-47.24, median=9.58; P<0.05).
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PMID:Chemiluminescent determination of leukocyte alkaline phosphatase: an advantageous alternative to the cytochemical assay. 1738 76


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