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

We have assessed levels of surface-expressed complement regulatory proteins, decay-accelerating factor (DAF) and membrane cofactor protein (MCP) on cells from patients with hematological malignancies. Neither malignant cells nor unaffected nucleated blood cells from the patients lacked MCP. On the other hand, complete deficiency of DAF was found in 2/10 of non-Hodgkin's lymphoma (NHL), while none of the 38 patients with acute nonlymphocytic leukemia (ANLL) (14 cases), chronic myelogenous leukemia (CML) (6 cases), acute lymphocytic leukemia (ALL) (12 cases) and chronic lymphocytic leukemia (CLL) (6 cases) lacked DAF. The two patients with DAF-negative NHL had no history of paroxysmal nocturnal hemoglobinuria (PNH), and their peripheral blood cells were DAF-positive. One DAF-negative NHL exhibited T cell markers and the other those of B cell. In both cases, treatment of the DAF-negative lymphoma cells with antibody against MCP (M177) followed by Mg(2+)-EGTA-serum resulted in efficient deposition of homologous C3. These results infer that some NHL specifically lack DAF and, through treatment with M177, are targeted by homologous C3.
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PMID:Deficiency of complement decay-accelerating factor (DAF, CD55) in non-Hodgkin's lymphoma. 172 75

We have developed a RIA for erythrocyte acid glutathione S-transferase (GST), which is immunologically identical to major GSTs from other blood cell components, and measured its serum concentrations in various hematological disorders. In some patients with paroxysmal nocturnal hemoglobinuria, chronic myelomonocytic leukemia, chronic myelocytic leukemia, polycythemia vera and myelofibrosis, the concentrations were high. Very high levels were found in 2 of 3 patients with acute lymphocytic leukemia, while acute myelocytic leukemia exhibited a modest increment. No or little increase was seen in aplastic anemia and myelodysplastic syndrome except chronic myelomonocytic leukemia. It is suggested that the measurement of serum acidic GST may be of use as a clinical marker of increased destruction and/or overproduction of blood cells.
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PMID:Radioimmunoassay for erythrocyte acidic GSH S-transferase. 249 36

Paroxysmal nocturnal hemoglobinuria (PNH) and the stable phase of chronic myelogenous leukemia (CML) are the two hematological conditions known to be associated with low levels of leukocyte alkaline phosphatase (LAP) activity in peripheral blood polymorphonuclear cells (PMN). LAP mRNA levels were determined in PMN from PNH and CML patients by RNA blotting analysis. In CML, LAP mRNA is undetectable, suggesting either decreased transcription or rapid degradation of the message. Contrarily, in PNH normal or high levels of LAP mRNA are present. This latter finding supports the concept of a deficit in the anchorage of the protein to the plasma membrane through the glycolipid pathway, even though other post-transcriptional mechanisms could be involved.
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PMID:Differences in the expression of alkaline phosphatase mRNA in chronic myelogenous leukemia and paroxysmal nocturnal hemoglobinuria polymorphonuclear leukocytes. 293 Aug 36

Three cases with chromosome changes involving bands 7p14 or 7p15 and 11p15 are described: one was a Japanese female with an acute myelomonocytic leukemia, the second was a white female with a 10-year history of paroxysmal nocturnal hemoglobinuria who developed a myelodysplastic syndrome, and the third was a patient with Ph-negative atypical chronic myelogenous leukemia with trisomy 8 and a chromosome change involving bands 7p14 and 11p15. These cases possibly indicate that the t(7;11)(p14 or p15;p15) change may characterize a subset of human nonlymphocytic neoplasia.
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PMID:Translocation between chromosomes 7 and 11 in nonlymphocytic neoplasia. 347 6

Marrow transplantation is effective treatment for a number of hematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is successful in the treatment of aplastic anemia with 70-85% long-term survival. It offers 10-30% apparent cures for patients with acute leukemia who have relapsed at least once, and for those with chronic myelocytic leukemia in blast crisis. Although still somewhat controversial, it appears to be the treatment of choice for patients with acute nonlymphoblastic leukemia in first chemotherapy induced remission, and for those with chronic myelogenous leukemia in the chronic phase since approximately 50-60% of these patients experience long-term, disease-free survival. Patients with acute lymphoblastic leukemia grafted in second or subsequent remission may expect a 30% "cure" of their disease. Marrow grafting is the only effective treatment for many patients with inherited immunologic deficiencies and certain genetic storage diseases. Cures of congenital Fanconi's anemia, Blackfan-Diamond anemia, osteopetrosis, paroxysmal nocturnal hemoglobinuria and thalassemia major have been achieved. Marrow transplantation is being explored for the therapy of patients with lymphoma, Hodgkin's disease, preleukemia, multiple myeloma, hairy cell leukemia, small cell lung cancer, testicular cancer, ovarian cancer and neuroblastoma. Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. More recently, marrow transplants from HLA-nonidentical family members and even from unrelated donors have been successfully explored.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Marrow transplantation: the Seattle experience. 391 47

Increased numbers of bone marrow mast cells were found in 45 (2.2%) of 2,000 bone marrow specimens obtained from patients who had hematologic disorders. Mast cells were most frequently seen in the marrows of patients who had preleukemic syndromes, lymphoproliferative disorders, and acute leukemia. The 16 patients who had preleukemic syndromes included those with refractory sideroblastic and megaloblastic anemia (with or without an excess of blasts), idiopathic pancytopenia or pure erythrocytic aplasia, paroxysmal nocturnal hemoglobinuria, idiopathic refractory neutropenia, agranulocytosis or thrombocytopenia, and persistent eosinophilia. Five of the seven patients who had acute leukemia had nonlymphoblastic leukemia; two had blastic crisis of chronic granulocytic leukemia. Of the 13 patients who had lymphoproliferative disorders, eight had chronic lymphocytic leukemia, three had macroglobulinemia, and two had non-Hodgkin's lymphoma. Three patients who had chronic renal failure associated with severe anemia and two who had chronic liver disease, splenomegaly, or hypersplenism were also encountered. In this study there appeared to be a consistent relationship between the presence of increased numbers of mast cells and the lymphocyte and plasma cell counts in the bone marrow. The significance of the presence of secondary mastocytosis in premalignant lesions, neoplasia, and, in particular, lympho- and myeloproliferative disorders, is still unclear.
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PMID:Increased bone marrow mast cells in preleukemic syndromes, acute leukemia, and lymphoproliferative disorders. 745 27

Expression of alkaline phosphatase (ALP) on the surface membrane of neutrophils (mNAP) was studied by immunofluorescence using an anti-ALP monoclonal antibody. Fluorescent intensity distribution of mNAP was analyzed using FACS (fluorescence-activated cell sorter). The mean fluorescent intensity (MFI) of the mNAP in this assay was well correlated with the neutrophil ALP (NAP) score demonstrated cytochemically (r = 0.832). mNAP levels in various hematological disorders were evaluated by % mNAP+ cells and MFI. The levels in aplastic anemia and polycythemia vera were significantly higher, and in chronic myelocytic leukemia and paroxysmal nocturnal hemoglobinuria (PNH), the levels were significantly lower compared with the levels in healthy volunteers. Two-color immunofluorescence with anti-ALP and anti-CD16 showed that the PNH clone was essentially negative for mNAP, whereas residual normal neutrophils (CD16+) had levels slightly higher than those in normal individuals. Highly reproducible results were obtained in the blood samples which were stored at 4 degrees C for at least 24 hr without any treatment prior to immunofluorescent staining. No degradation of fluorescent intensity was seen 4 days after staining and fixation. The mNAP assay is simple, without subjective evaluation for quantification, and is useful for differential diagnosis of hematological disorders.
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PMID:Assessment of alkaline phosphatase on the surface membrane of neutrophils by immunofluorescence. 988

Late clonal complications of aplastic anemia (AA) such as acute leukemia, myelodysplastic syndromes or paroxysmal nocturnal hemoglobinuria have been recognized for a long time. To our knowledge, chronic myelogenous leukemia (CML) as a late complication of severe aplastic anemia has as yet not been reported. We report here a case of AA treated successfully with antilymphocytic globulin and cyclosporin in whom Ph1 negative, BCR/ABL negative CML developed 8 years after diagnosis of AA. This case of atypical, secondary CML was refractory to treatment with interferon alpha and hydroxyurea.
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PMID:Atypical chronic myelogenous leukemia following immunosuppressive therapy for severe aplastic anemia. 1051 77

Haematopoiesis can be interpreted as an ecosystem composed of billions of cells interacting according to Darwinian rules. Mutation, by promoting cell diversity, ensures versatility in coping with internal and external challenges. Most mutated cells are eliminated through apoptosis. However, if mutation generates relative resistance to apoptosis it may result in growth advantage for the mutated cells. The probability of monoclonality and malignancy is significantly increased if the normal multiclonal environment is damaged by a pathologic proapoptotic process that spares the apoptosis resistant clones. Paroxysmal nocturnal haemoglobinuria, myelodysplastic syndromes, chronic myeloid leukaemia, secondary acute leukaemias and immunosuppression-related non-Hodgkin's lymphomas can be interpreted as 'opportunistic' clonal and malignant diseases. Free radicals (FRs) are closely linked to apoptosis and have been incriminated in oncogenesis. Conditions associated with increased FR formation or impaired FR disposal may provide the enhanced apoptotic background against which an apoptosis-resistant clone may gain growth advantage.
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PMID:Cell darwinism, apoptosis, free radicals and haematological malignancies. 1113 55

The Cord Blood Transplantation study group conducted a prospective study of unrelated cord blood transplantation (CBT) to better define the role of this stem cell source for subjects requiring unrelated allogeneic transplantation. We report on 1 stratum of the study designated for adult subjects. The primary end point of the study was survival at 180 days. Secondary end points included engraftment, graft-versus-host disease, relapse, and long-term survival. Eligibility criteria for malignant and nonmalignant diseases were specified. Subjects with active central nervous system disease, Karnofsky performance status <70%, grade 3 or 4 or primary myelofibrosis, or suitable related donors were excluded. Enrollment required a single cord blood unit containing >10(7) nucleated cells per kilogram of recipient weight and matched at > or =4 HLA-A and -B (low or intermediate resolution) and -DRB1 (high resolution) types. Thirty-four subjects were entered, with a median age of 34.5 years (range, 18.2-55 years). Most subjects (n = 23) had a 4 of 6 match, 10 subjects had a 5 of 6 match, and 1 subject had a 6 of 6 match. Diagnoses at transplantation included acute myelogenous leukemia (n = 19), acute lymphoblastic leukemia (n = 9), chronic myelogenous leukemia (n = 3), myelodysplastic syndrome (n = 1), paroxysmal nocturnal hemoglobinuria (PNH) (n = 1), and non-Hodgkin lymphoma (n = 1); 94% were classified as poor risk according to National Marrow Donor Program criteria. Subjects received total body irradiation/cyclophosphamide (n = 27) or busulfan/melphalan (n = 7) conditioning regimens. Four subjects died before CBT and are described here but are not included in the main analysis. The cumulative incidence rates and median times to neutrophil (500/microL) and platelet (>20,000/microL) engraftment were 0.66 by day 42 (median, 31 days) and 0.35 by day 180 (median, 117 days). The cumulative incidence rate for grade II-IV GVHD was 0.34 by day 100. For the primary end point, survival at 180 days, Kaplan-Meier survival estimates were 0.30 (95% confidence interval, 0.14-0.46) by day 180 after transplantation. To date there are 2 survivors, and both are >36 months from enrollment. A retrospective analysis was performed by using high-resolution HLA-A and -B typing, which revealed that approximately one third of subjects had 1 or more additional HLA mismatches compared with results of low- or intermediate-resolution HLA typing. The findings of high treatment-related mortality and slow engraftment kinetics indicate that CBT should continue to be performed in specialized centers with a research focus on cord blood cells.
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PMID:Umbilical cord blood transplantation in adults: results of the prospective Cord Blood Transplantation (COBLT). 1568 76


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