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)

A 32-year-old male presented with isolated neutropenia 6 months after allogeneic bone marrow transplantation for CML from his HLA-matched brother. The presence of granulocyte-specific IgM and IgG antibodies in the patient's serum indicated an immune-mediated basis for the neutropenia. A variety of manoeuvres to suppress antibody production or to reduce peripheral destruction, including high-dose intravenous immunoglobulins 400 mg/kg (total 24 g) on 5 consecutive days, prednisolone 80 mg for 10 d and plasmapheresis on 3 consecutive d, failed to raise the neutrophil count. Splenectomy, however, resulted in a prompt and sustained rise of neutrophils to normal values.
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PMID:'Auto'-immune neutropenia after allogeneic bone marrow transplantation unresponsive to conventional immunosuppression but resolving promptly after splenectomy. 304 20

Bone marrow transplantation is impossible without effective support with blood components during the period of pancytopenia before graft function appears. We analyzed 39 patients with leukemia and three patients with severe aplastic anemia with regard to the pre- and postgrafting requirements for RBC and PLT transfusions. Overall a median of eight RBC and four PLT concentrates were necessary in all 42 patients after allogeneic BMT (ranges, 1-32 RBC and 1-11 PLT units). Requirements were identical irrespective of the underlying disease (ALL, AML, CML, SAA). Transfusion need for RBC and PLT concentrates increased in patients over 30 years old and with a major red blood group AB0 barrier between marrow donor and recipient. The presence of grade II-IV GvHD increased RBC requirements significantly, but not PLT requirements. In addition these patients were dependent on RBC transfusions for significantly longer periods. Only one patient required therapeutic granulocyte transfusions. In a CMV-negative patient with a CMV-negative marrow donor, who died of veno-occlusive disease, cytomegalovirus was transmitted inadvertently by a seropositive PLT concentrate in his final course. Our transfusion strategy included frozen deglycerolized RBC concentrates and single donor PLT concentrates, collected mainly from the marrow donor by a cell separator. All blood products were irradiated in vitro with 1500 cGy before transfusion. An optimal transfusion policy starting before BMT can contribute to successful bone marrow transplantation.
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PMID:Hematological support in patients undergoing allogenetic bone marrow transplantation. 305 Dec 11

To evaluate the membrane marker profile of human basophils a panel of well-established monoclonal antibodies (MoAbs, n = 60) was used for a combined toluidine/immunofluorescence staining procedure. Myeloid-associated MoAbs (particularly MoAbs against the LFA-1 family (CD11, CDw18), MoAbs directed against lactosylceramide (CDw17), anti-glycoprotein (gp) 150 MoAbs MCS 2 and MY 7 (CDw13), anti-gp 67 MoAb MY 9, anti Fc gamma-receptor (mol wt 40 kd) MoAb CIKM5, anti-CR 1 MoAb E 11, and the antiglycolipid MoAb VIM-2) were reactive with basophils, indicating a close relationship to other mature myeloid cells. Under normal conditions, basophils surprisingly express at least three activation-linked structures not detectable on mature neutrophils, ie, the p45 structure defined by MoAbs OKT-10 and VIP-2b, the p24 structure identified by the CD9 MoAb BA-2, and the receptor for interleukin 2 (IL 2) recognized by three different MoAbs (anti-TAC, IL2RI, anti-IL 2). Moreover, under short-term culture conditions basophils both in mononuclear cell (MNC) suspension and as purified fractions display the HLA-DR and T4 antigens. The neutrophilic/eosinophilic structure 3-fucosyl-N-acetyllactosamine is expressed on basophils only after neuraminidase treatment. Basophils were not stained at all by CD 16 MoAbs directed against the Fc gamma-receptor (mol wt 50 to 70 kd) of neutrophils, by the MoAb 63D3 (CDw12) recognizing the monocyte/granulocyte-associated p 200 antigen, and by the CDw 14 antibodies (VIM-13, Mo 2) defining the monocyte-specific structure p 55. Enriched basophils freshly obtained from chronic granulocytic leukemia (CGL) patients yielded identical results in FACS analyses. In summary, these data indicate that basophils generate a unique combination of surface determinants and possibly represent an activated cell population.
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PMID:Human blood basophils display a unique phenotype including activation linked membrane structures. 311 89

Butyric acid has been shown to inhibit the growth of several established tumor cell lines and to induce either granulocytic or erythroid differentiation in different human and murine leukemic cell lines. The dose-dependent effect of butyric acid was tested in vitro on the clonal growth of granulocyte macrophage progenitors in 13 patients with chronic myeloid leukemia (CML) and compared with control bone marrow and peripheral blood responses. The growth of myeloid progenitors from both healthy donors and non-leukemic and leukemic patients was almost completely inhibited by 1.0 mM butyric acid. At 0.5 mM butyric acid, inhibition of CML progenitors, both from chronic phase and blastic phase patients, was significantly greater (P less than 0.01) than bone marrow from non-leukemic patients and peripheral blood controls. Butyric acid, a 4-carbon compound, was the most potent inhibitor of six short chain fatty acids tested on CML myeloid progenitors.
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PMID:Butyric acid: inhibition of non-leukemic and chronic myeloid leukemia granulocyte macrophage clonal growth. 319 30

Peripheral blood lymphocytes (PBL) from chronic myeloid leukemia (CML) patients in remission were stimulated in vitro, in a 3-cell assay with autologous leukemic cells or autologous bone marrow (BM) cells alone, or each in combination with allogeneic PBL. The responder cells were used as effectors in a 4-h 51Cr release cytotoxicity assay using autologous targets such as leukemic cells, BM cells, phytohemagglutinin-induced lymphoblasts, and allogeneic K562 (erythroblastoid leukemic cell line) target cells. Sensitization of lymphocytes from CML patients with either autologous leukemic cells or BM cells generated cytotoxic cells (CTCs) capable of killing both the targets. These results suggested that in CML, the PBL may have been sensitized to myeloid maturation-releated antigens in vivo, which, on secondary stimulation in vitro, may result in differentiation of CTCs cytotoxic to immature myeloid cells, either from autologous leukemic cells or autologous BM. The inability of PBL from patients with oral cancers to lyse autologous BM cells upon in vitro stimulation, supported this possibility. Clonogenic assays conducted to assess the colony forming potential of BM cells which had interacted with CTCs indicated that there was about 37% reduction in committed granulocyte stem cell colony formation without an appreciable change in committed granulocyte/monocyte stem cell units and clusters. Therefore, since the BM toxicity of the CTCs is not very high, these cells may have a potential clinical use in CML.
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PMID:In vitro generation of effector cells cytotoxic to autologous targets from chronic myeloid leukemia patients in remission. 326 14

Marrow and peripheral blood cells from nine children with juvenile chronic granulocytic leukemia (JCGL) demonstrated intense (94 +/- 16% maximum) spontaneous granulocyte/macrophage colony growth but cells from five children with the adult variety of CGL did not. This unusual pattern of colony growth depended upon a stimulatory protein(s) produced by mononuclear phagocytes. No GM-CSA activity was found in any chromatofocused fraction of JCGL monocyte-conditioned media but an activity that induced GM-CSA in umbilical vein endothelial cells was detected at pI 6.9-7.2. Moreover, the CSA-inducing monokine was neutralized by an anti-IL-1 antibody in vitro and, in the one case so tested, the same antibody also inhibited "spontaneous" colony growth. Therefore granulocyte/macrophage colony growth in JCGL is characteristically abnormal and distinguishes JCGL from the adult form of the disease. This abnormality depends upon the production, by mononuclear phagocytes, of IL-1 which, in turn, stimulates the release of high levels of colony stimulating activity by other cells. The high proliferative activity of CFU-GM we found in JCGL patients, and the high levels of GM-CSA found in their serum are compatible with the view that the in vitro abnormality reflects a similar abnormality in vivo.
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PMID:Interleukin 1-dependent paracrine granulopoiesis in chronic granulocytic leukemia of the juvenile type. 326 28

Bone marrow aspirates from healthy donors contain a fraction of low density multicellular spheroids, 100-500 microns in diameter. They are organized in a three-dimensional network consisting of central preadipocytes/adipocytes, mesenchymal and reticular cells, and resident macrophages that are closely associated with myeloid, erythroid and megakaryocyte progenitor cells and with their progenies. These spheroids are 2- to 5- fold more abundant in progenitor cells compared with the whole bone marrow as estimated by monoclonal antibody markers My 10 and T 9, by analysis of granulocyte--macrophage colony forming cells (GM-CFC) and by cytological techniques. They produce terminally differentiated cells in organotypic microcultures. We suggest that a multicellular spheroid may represent the fundamental unit of primary hematopoiesis; we therefore name it hematon. Here we show that the presence of hematons in bone marrow aspirates correlated positively with homeostatic blood cell production: they were present in normal bone marrow (BM) (19/25), and absent in myelodysplasic syndromes (MDPS) (8/21), in acute nonlymphocytic leukemias (ANLL) (3/22) and in chronic myeloid leukemia (CML) (2/28). The hematons were recovered under hematological remission in MDPS and in ANLL, suggesting that they may be dispersed reversibly in certain disease conditions. The hematons represent a unifying model around which the variability in some bone marrow cell functions can be explored.
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PMID:Hematon: a multicellular functional unit in primary hematopoiesis. 326 80

A combined high-performance liquid chromatography-sodium dodecyl sulfate-gel electrophoresis method for the study of the phenotypic protein patterns of mature blood granulocytes was previously described. With the use of this method in the present study, the progression of human chronic myelogenous leukemia (CML) from the stable to the blast crisis stage was shown to be accompanied by a progressive decrease in the amounts of cell membrane and granule phenotypic proteins in mature granulocytes. Survival time from the initial diagnosis was significantly shorter for CML patients whose levels of granulocyte phenotypic proteins were below the normal range compared with survival time for those patients whose levels were normal or higher than normal. The data suggest that these changes in mature granulocytes serve as useful diagnostic indicators of an impending blast crisis in CML patients.
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PMID:Progressive loss of phenotypic proteins in mature granulocytes before the onset of blast crisis in human chronic myelogenous leukemia. 328 Aug 10

Chromosome studies of cells from megakaryocytic colonies (CFU-Meg) as evidenced by a megakaryocyte-specific monoclonal antibody, TP80, from a patient with chronic myelogenous leukemia (CML) in the blast crisis (BC) revealed the same aberrant karyotype, 52,XY,+9,+9,+18,+19,+21,+22,t(9;22)(q34;q11),t(9;22), as that having newly appeared in the peripheral blood. Cells from erythroid bursts (BFU-E) showed only the standard 46,XY,t(9;22) karyotype, and cells from granulocyte/macrophage colonies (CFU-GM) had either of these karyotypes. These results demonstrated that the whole megakaryocytic line and part of the granulocyte/macrophage line had been involved in the BC while the erythroid line totally belonged to the original clone. Chromosome analysis coupled with immunophenotyping of hemopoietic colonies was useful for a definite diagnosis of megakaryoblastic crisis of CML in this patient.
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PMID:Chromosome studies of hematopoietic colonies for distinct diagnosis of megakaryoblastic crisis of chronic myelogenous leukemia: a case report. 330 67

Eight patients with haematologic malignancies contracted fatal invasive aspergillosis during an outbreak. Five patients were neutropenic. Bronchofiberoscopic examination with microbiology specimen brush and bronchoalveolar lavage yielded Aspergillus fumigatus in only 2/5 patients examined. The specific diagnosis reached during lifetime in 5 patients was based on a combination of invasive procedures (lung biopsy in 2, percutaneous lung puncture in 1), the presence of a lung abscess (3 patients), seroconversion (1 patient), and purulent maxillary sinusitis caused by A. fumigatus together with repeated abundant growth of A. fumigatus in the sputum (1 patient). Six patients received amphotericin B. The infection was temporarily controlled only in 2 bone marrow transplant recipients whose granulocyte counts recovered. In 3/8 patients the pneumonia was of polymicrobial aetiology, Mycobacterium tuberculosis (2 patients), Pneumocystis carinii (1 patient), and Legionella pneumophila (1 patient) being the other microbes involved. 3/4 bone marrow transplant recipients with aspergillosis had been transplanted for chronic myeloid leukaemia, supporting the previously reported association of bone marrow transplantation for chronic myeloid leukaemia and the risk of invasive aspergillosis. Improved diagnostic methods for earlier definitive diagnosis of invasive aspergillosis as well as more efficacious and less toxic antifungal agents are needed to allow early treatment.
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PMID:Invasive pulmonary aspergillosis: a diagnostic and therapeutic problem. Clinical experience with eight haematologic patients. 332 14


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