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)

Interferon alpha (INF-alpha)--In systemic diseases, most indications for INF-alpha result from its effect on haematological or hepatological manifestations. The spectacular effect of INF-alpha in chronic myeloid leukemia has led to its use for the treatment of hypereosinophilia syndrome and systemic mastocytosis. Over the last 6 years, we have treated 7 patients with the hypereosinophilia syndrome who were resistant to corticotherapy and had markers of myeloproliferation. Although both hydroxyurea and INF-alpha can be effective alone, their combination led to a decrease in the eosinophilia count to 1,000/ml, a decrease which was long-lasting in most cases. INF-alpha is also used in histiocytosis X alone or in combination with retinoids or with etoposide and has been found effective in several observations. In carcinoid syndromes whether treated priorly or not with a 5-fluoro-uracil-streptozoticin combination, INF-alpha leads to an objective response in two-thirds of the patients. Several multicentric protocols are currently assessing the efficacity of INF-alpha in mixed cryoglobulinaemias. In most observations these cryoglobulinaemias are seen in patients with markers of hepatitis C (mainly HCV) and the early results are encouraging. Temporary improvement has been reported in discoid or subacute lupus in 8 out of 10 cases. Haemangiomas of the infant, when life-threatening and corticoresistant, may be a good indication for INF-alpha. Thus 20 newborns or infants (including 4 with Kasabach-Merrit syndrome) have been treated with good results in 18. Interferon gamma (INF-gamma).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Interferons. Interferons alpha and gamma: indications in systemic diseases]. 817 44

We report two cases of Philadelphia chromosome (Ph)-positive acute leukemia with definite myeloid markers. Ph was the sole chromosomal abnormality at presentation, and neither eosinophilia, basophilia, thrombocytosis nor hepatosplenomegaly was present. In both cases, Ph+ myeloblasts showed positive stain for myeloperoxidase and naphthol ASD chloroacetate esterase, which fulfilled the FAB criteria of acute myelogenous leukemia (AML). Ph+ myeloblasts co-expressed myeloid and B-lymphoid antigens (CD10, CD13, CD19 and CD33). In case 1, myeloblasts rearranged M-BCR, and the expression of M-BCR/ABL chimeric RNA was demonstrated by using the reverse transcription polymerase chain reaction (RT-PCR). They also clonally rearranged IGH. Ph clone disappeared on cytogenetic analysis in remission, and granulocytes in remission did not have rearranged M-BCR. In case 2, morphocytochemically distinct myeloid and lymphoid blast populations were seen. Myeloblasts and lymphoblasts were enriched > 96% as CD19-/CD33+ and CD19+/CD33- populations, respectively. Both of them possessed the identical rearrangement of IGH and M-BCR, indicating a common leukemic progenitor cell origin. Furthermore, m-BCR/ABL was detected in addition to M-BCR/ABL on RT-PCR. Accordingly, both cases were diagnosed as de novo Ph+ acute leukemia rather than as chronic myelogenous leukemia in blastic crisis. Their mixed B-lymphoid/myeloid characteristics strongly suggest that so-called 'Ph+ AML' is derived from Ph+ myeloid/B-lymphoid stem cells.
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PMID:B-lymphoid/myeloid stem cell origin in Ph-positive acute leukemia with myeloid markers. 832 35

We have isolated and sequenced a 598-bp full length cDNA clone for the human Charcot-Leyden crystal (CLC) protein (eosinophil lysophospholipase), the unique and prominent constituent of human eosinophils and basophils that forms the hexagonal bipyramidal crystals classically observed in tissues and secretions from sites of eosinophil-associated inflammation. A 426-bp open reading frame encoded a 142-amino acid polypeptide with a predicted molecular mass of 16.5 kDa and isoelectric point of 7.28. The deduced amino acid sequence of CLC protein showed 20 to 30% similarity over regions of approximately 100 amino acids with the carboxyl-terminal domains of four IgE-binding proteins, including the 31-kDa human and rat IgE-binding proteins, the 35-kDa mouse carbohydrate binding protein (CBP35), Mac-2, the murine macrophage cell surface protein that is identical to CBP35, and the human homologue of Mac-2. These proteins are members of a superfamily of beta-galactoside binding S-type animal lectins, which includes a group of highly conserved 14-kDa lectins isolated from human lung, heart, placenta, bovine heart, chicken skin, mouse fibroblasts, and the electric organ of the electric eel; CLC protein also showed sequence similarities to these 14-kDa animal lectins, including conservation of 7 of 16 invariant amino acid residues thought to comprise the carbohydrate-binding domain of these proteins, with conservative amino acid changes at others; thus, CLC protein could potentially possess carbohydrate or IgE-binding activities. Northern analyses revealed an approximately 900-bp mRNA species that was present in peripheral blood eosinophils from patients with eosinophilia, basophils from patients with chronic myelogenous leukemia, and in HL-60 cells induced towards eosinophilic differentiation with B cell growth factor-II (IL-5) or granulocytic differentiation with DMSO, but was absent in neutrophils, monocytes, T cells, B cells, or HL-60 cells induced towards monocytic differentiation with vitamin D3. Southern analyses revealed a gene of approximately 5 to 6 kb in length. The cDNA clone and complete amino acid sequence data for CLC protein will facilitate structure-function analyses of its unusual hydrophobic properties, unique propensity for crystallization, lysophospholipase, and potential lectin-like activities.
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PMID:Molecular cloning and characterization of human eosinophil Charcot-Leyden crystal protein (lysophospholipase). Similarities to IgE binding proteins and the S-type animal lectin superfamily. 841 78

The in vivo kinetics of autologous 111In-oxine labeled eosinophils were studied in 3 patients with reactive eosinophilia. Organ distribution and life span of 111In-oxine labeled eosinophils were evaluated. The disappearance curve of the labeled eosinophils showed two exponential components in all cases. Between these two factors, there was a slightly increase of radioactivity, suggesting the presence of recirculation. Radioactivity in the spleen, the liver and the bone marrow were observed 5 minutes after the infusion, suggesting the presence of marginal pool in these organs. Radioactivity in the spleen was increased rapidly during 1 and 24 hours after the infusion. Sequestration and/or destruction of increased eosinophils may exist in the splenic pool. The granulocyte turnover rate in eosinophilia was less than in CML or chronic neutrophilia. The results indicate that the migration of eosinophils is less active than that of neutrophils.
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PMID:[Eosinophil kinetics]. 849 52

Hematological malignancies accompanied by eosinophilia are reviewed in relation to chromosomal changes and cytokine production. Eosinophilia accompanied by hematological malignancies can be divided into two groups. In some myelogenous leukemias, including acute myelomonocytic leukemia with eosinophilia (FAB M4Eo), acute myeloblastic leukemia (FAB M2 t(8;21)) and chronic myelogenous leukemia, neoplastic cells themselves appear to differentiate into eosinophils. On the other hand, transformed tumor cells secrete some eosinophil-stimulating cytokines, including interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor and these cytokines stimulate the proliferation of normal eosinophil precursors in some lymphoid malignancies, including some types acute lymphoblastic leukemia (especially with t(5;14)) or malignant lymphoma, including Hodgkin's lymphoma and adult T cell lymphoma/leukemia.
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PMID:[Hematological malignancies with eosinophilia]. 849 61

Many hematologic disorders present minimal physical signs and symptoms in the early state. For example, chronic myelogenous leukemia may not manifest splenomegaly or any obvious physical signs, yet the laboratory report may demonstrate leukocytosis, eosinophilia, basophilia, and thrombocytosis. Although the anemic condition of a patient with a hemoglobin level of 7 gm/dl may be readily apparent to the clinician, a hemoglobin level of 10.5 gm/dl may be difficult to discern during a brief visit that is focused on another organ system. The same laboratory report, however, may contain valuable clues about unsuspected anemia related to mean corpuscular volume or morphology. Information from supporting chemistry studies often may be helpful in interpretation of the diagnosis. An elevated uric acid level, for example, may indicate hyperkinetic cytogenesis related to myeloproliferative or lymphoproliferative neoplastic disorders. This monograph is designed to be useful to busy physicians who want to use basic hematologic studies in a cost-effective manner. Hematology is viewed in a problem-oriented way; the laboratory report is used as the problem generator.
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PMID:Hematology for primary care physicians. 860 64

Hypereosinophilic syndromes may result either from eosinophilic differentiation of a clone of neoplastic cells or from reactive eosinophilia. In other patients HES is idiopathic. It appears likely that in many patients the "idiopathic' hypereosinophilic syndrome is actually a chronic myeloproliferative disorder. Those cases showing an increase of blast cells or a demonstrable clonal cytogenetic abnormality should be classified as eosinophilic leukaemia. In other cases the neoplastic nature of the disease can be recognized only in retrospect when a granulocytic sarcoma or AMI, develops. A few cases of idiopathic HES are consequent on cytokine secretion whereas others remain idiopathic at the time of death. When eosinophilia occurs as a feature of an acute or chronic myeloid leukaemia or a chronic myeloproliferative disorder the eosinophils are usually part of the leukaemic clone. However, eosinophilia in association with acute lymphoblastic leukaemia is usually reactive. Rare cases have a biphenotypic leukaemia/lymphoma with both eosinophils and lymphoid cells arising from a mutant pluripotent stem cell.
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PMID:Eosinophilic leukaemias and the idiopathic hypereosinophilic syndrome. 885 31

The 12- to 14-kDa eosinophil major basic protein (MBP) is primarily translated as 25-kDa pro-MBP. HL-60, a promyelocytic leukemia cell line, produces pro-MBP but not MBP, suggesting production of pro-MBP by immature granulocytes. We measured the serum levels of total MBP, using an ELISA that detects both pro-MBP and MBP, in 25 patients with leukemia (six acute myelogenous leukemia (AML), seven acute lymphoblastic leukemia (ALL), eight chronic myelogenous leukemia (CML), four chronic lymphocytic leukemia (CLL)) and five recipients of allogeneic bone marrow transplants (BMT). None of these patients except one AML (M4Eo) showed eosinophilia. Serum levels of total MBP were elevated in all the patients with CML and AML, but not in any of those with ALL or CLL. In all four recipients of BMT who obtained engraftments, serum levels of total MBP started to increase 12-14 days after BMT and reached the highest levels (4-10 times the basal levels) at days 19-32. In a recipient of BMT who did not obtain an engraftment, serum levels of total MBP were not increased. These findings suggested that pro-MBP could be used as a marker for proliferation of immature granulocytes with normal or malignant nature.
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PMID:Elevated serum levels of eosinophil major basic protein in patients with myeloproliferative disorders without eosinophilia. 927 50

We present the case of a two-year-old child with an atypical presentation of chronic myeloid leukemia. At diagnosis, he showed clinical and biological features of juvenile chronic myeloid leukemia (CML). However, eosinophilia was observed in blood and bone marrow. The bone marrow karyotype did not demonstrate the Philadelphia chromosome but BCR-ABL rearrangement was shown to be present by reverse transcriptase polymerase chain reaction (RT-PCR) analysis and confirmed by fluorescent in situ hybridization (FISH) analysis. Discussion centres on the differentiation between juvenile CML and childhood chronic myelogenous Leukemia and the importance of carrying out RT PCR for all juvenile CML cases.
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PMID:Philadelphia negative BCR-ABL positive chronic myeloid leukemia mimicking juvenile chronic myeloid leukemia in a 2-year-old child. 938 69

An animal model of chronic myeloid leukemia (CML) will help characterize leukemic and normal stem cells and also help evaluate experimental therapies in this disease. We have established a model of CML in the NOD/SCID mouse. Infusion of > or = 4 x 10(7) chronic-phase CML peripheral blood cells results in engraftment levels of > or = 1% in the bone marrow (BM) of 84% of mice. Engraftment of the spleen was seen in 60% of mice with BM engraftment. Intraperitoneal injection of recombinant stem cell factor produced a higher level of leukemic engraftment without increasing Philadelphia-negative engraftment. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor did not increase the level of leukemic or residual normal engraftment. Assessment of differential engraftment of normal and leukemic cells by fluorescence in situ hybridization analysis with bcr and abl probes showed that a median of 35% (range, 5% to 91%) of engrafted cells present in the murine BM were leukemic. BM engraftment was multilineage with myeloid, B-cell, and T-cell engraftment, whereas T cells were the predominant cell type in the spleen. BM morphology showed evidence of eosinophilia and increased megakaryocytes. We also assessed the ability of selected CD34+ CML blood cells to engraft NOD/SCID mice and showed engraftment with cell doses of 7 to 10 x 10(6) cells. CD34- cells failed to engraft at cell doses of 1.2 to 5 x 10(7). CD34+ cells produced myeloid and B-cell engraftment with high levels of CD34+ cells detected. Thus, normal and leukemic stem cells are present in CD34+ blood cells from CML patients at diagnosis and lead to development of the typical features of CML in murine BM. This model is suitable to evaluate therapy in CML.
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PMID:Establishment of a reproducible model of chronic-phase chronic myeloid leukemia in NOD/SCID mice using blood-derived mononuclear or CD34+ cells. 942 19


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