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)

We have produced a monoclonal antibody (MoAb), AML-1-99, that defines a novel 124-kd protein antigen expressed on a subpopulation of monocytes and on the majority of hematopoietic progenitor cells of the granulocyte-monocyte (CFU-GM), erythroid, and mixed-lineage classes. AML-1-99 is lytic to bone marrow (BM)- and peripheral blood-derived progenitor cells in the presence of rabbit complement (C'). AML-1-99 is not toxic to progenitor cells in the absence of C', nor does it modify their growth when included in colony-forming cultures. Several leukemia cell lines, including HL-60, U937, KG-1a, and Daudi cells, express the antigen on the majority of cells. Freshly isolated leukemia cells from patients with acute myelogenous leukemia (AML) react variably with AML-1-99. Leukemia colony-forming cells from several AML patients express the antigen and could be eliminated by treatment with AML-1-99 and C'. Cell sorting and immune rosette techniques were successfully applied to normal BM and chronic myelocytic leukemia cell populations using AML-1-99 with the result that significant enrichment of CFU-GM could be accomplished. The pattern of reactivity of this MoAb and its apparent molecular weight suggests that AML-1-99 recognizes a newly defined myeloid-associated cell surface antigen.
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PMID:Distribution of the 124-kd antigen defined by monoclonal antibody AML-1-99 on normal and leukemic myeloid cells. 342 92

A novel sialylated fucosyl glycolipid, which is present at an elevated level in chronic myelogenous leukemia cells, was isolated. The structure of this fucoganglioside was elucidated by methylation analysis, fast atom bombardment-mass spectrometry, and enzymatic degradation, followed by reaction with anti-Lex, Gal beta 1----4 (Fuc alpha 1----3) GlcNAc beta 1----, monoclonal antibody. The structure of this ganglioside was found to be: (Formula: see text). This structure is unique in that a fucose is attached to the internal N-acetylglucosamine but not to the subterminal N-acetylglucosamine. Since this glycolipid is apparently absent in normal granulocytes or acute myelogenous leukemia cells, it can be a specific marker for chronic myelogenous leukemia cells. Based on the structures of this fucoganglioside and normal granulocyte glycolipids, a biosynthetic pathway of extension, sialylation, followed by fucosylation is proposed.
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PMID:Structure of a novel sialylated fucosyl lacto-N-norhexaosylceramide isolated from chronic myelogenous leukemia cells. 345 27

The expression of HLA-DR antigens by normal myeloid progenitor cells (CFU-GM) has been linked to inhibition of colony growth by prostaglandin E (PGE), while resistance to the inhibitory effects of PGE in chronic myeloid leukemia (CML) has been attributed to a lower fraction of HLA-DR+ CFU-GM in this disease. However, we have previously shown that virtually all CFU-GM in normal bone marrow (NBM) as well as CML peripheral blood express HLA-DR antigens, which raises the possibility that these surface molecules may not be the sole determinants of a progenitor cell's sensitivity to PGE. In order to evaluate the relationship between HLA-DR expression and prostaglandin inhibition, we partially purified NBM progenitor cells using fluorescence-activated cell sorting to prepare cell fractions with high and low HLA-DR antigen density. Normal progenitor cells with high DR density tended to form monocyte colonies in agar culture, whereas the low DR density fraction was enriched for granulocyte colony-forming cells. Inhibition by PGE was greatest in the high DR+ fraction and was largely restricted to monocyte progenitor cells. Inhibition of CFU-GM by PGE was less in CML than in NBM, but this decreased inhibition correlated with a significantly lower number of monocyte-CFU in CML. These data suggest that high HLA-DR antigen density may select for normal progenitor cells that are committed to monocyte differentiation and are, therefore, more likely to be inhibited by PGE. The relative deficit of monocyte progenitor cells in CML may partially explain the phenomenon of PGE resistance in this disease.
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PMID:Relationship between HLA-DR expression by normal myeloid progenitor cells and inhibition of colony growth by prostaglandin E. Implications for prostaglandin E resistance in chronic myeloid leukemia. 345 31

Myeloid cytoreduction leading to hematologic remissions is frequently seen among patients with chronic phase Philadelphia-positive chronic myelogenous leukemia (CML Ph') treated with leukocyte interferon (IFN-alpha). In order extend our understanding of the events associated with interferon-induced myeloid cytoreductions, we have examined the changes in granulocyte-monocyte colony-forming cells (GM-CFC) in such CML Ph' patients. A total of 28 CML Ph' patients in hematologic remissions following IFN-alpha treatment had a median GM-CFC of 12 (range, 0-182)/1 X 10(5) bone marrow cells. This was significantly lower than the median GM-CFC of 104 (range, 44-815; p less than 0.01) in 22 untreated or minimally treated CML Ph' patients and the median of 72 (range, 30-204; p less than 0.05) in 18 normal controls. A gradual decline in the GM-CFC numbers from a median of 105 to a median of 1.8 was seen in six responding patients who were studied serially over a median period of 7.5 months. In these patients, we also observed a profound decline in the number of aspirated bone marrow nucleated cells and a decline in the bone marrow cellularity. The effect of treatment interruption for a median of 13 days was studied in five patients. In three of the patients who had received IFN-alpha for less than or equal to 6 months, treatment interruption resulted in rapid increase in the GM-CFC, while the GM-CFC did not change in the remaining two patients, who received IFN-alpha for one and two years. We conclude that treatment of CML patients with IFN-alpha resulted in a progressive decline of the bone marrow GM-CFC. The initially expanded pool of committed myeloid stem cells declines gradually, and at the time of hematologic remission the number of GM-CFC/10(5) nucleated bone marrow cells is lower than that of normal controls. In the early phases of IFN-alpha treatment, this inhibitory effect is rapidly reversible, but it seems to persist when the treatment is extended over more than one year.
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PMID:Changes in granulocyte-monocyte colony-forming cells among leukocyte-interferon-treated chronic myelogenous leukemia patients. 346 Aug 11

Mixed leukocyte suspensions were prepared from heparinized blood collected from healthy subjects and from patients with chronic myeloid leukemia (CML). In all the suspensions determinations were made for: zinc, by atomic absorption; granulocyte alkaline phosphatase (GAP), using the method with p-nitrophenylphosphatase; granulocyte LDH, by means of the enzymatic autoanalyser LKD 8,600. In the patients with CML, the values of zinc and of granulocyte alkaline phosphatase activity were very low while the granulocyte LDH values were higher than normal. The chromatogram of the granulocyte LDH isoenzymes on DEAE-Sephadex A50 minicolumn (0.5 X 12 cm) showed an "alpha type abnormality" revealed by the increased activity of the isoenzymes with high electrophoretic mobility LDH2 and LDH1 specific for tissues with intense oxidative phosphorylation. In the normal subjects the chromatogram of the leukocyte LDH isoenzymes showed a type M (skeletal muscle) prevalence denoting intense anaerobic glycolysis. Therefore the low zinc concentrations (0.55 micrograms mg N2 as compared with the normal 1.24 micrograms mg N2) in these patients cause the decrease of GAP activity by the lack of zinc in the active center of the enzyme and the decrease of cellular permeability thus allowing the extracellular release of granulocyte LDH.
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PMID:Study of the relationship between the granulocyte LDH, alkaline phosphatase and Zn at the level of the leukocyte in patients with chronic myeloid leukemia. 346 14

To study the feasibility of using retroviruses for gene transfer into human hemopoietic cells, various cell types were exposed to virus carrying the gene for neomycin resistance (neor). In preliminary studies using K562 cells as targets, we found that high viral titer and co-cultivation with viral producer cells rather than incubation in medium exposed to viral producer cells were important variables for achieving high frequencies of G418 resistant (G418r) colonies. The maximum frequency of G418r K562 colonies after co-cultivation with cells producing a neor virus titer of 4 X 10(6) cfu/mL was 60%. When primary human progenitors from normal marrow, fetal liver, or chronic myelogenous leukemia blood were exposed to high titer viral stocks, both with and without helper virus, under conditions optimized for K562 cells, maximum frequencies of G418r colonies were 3% to 16% for granulocyte macrophage progenitors and 2% to 6% for primitive erythroid progenitors. The presence of the neor gene in both G418r K562 and primary hemopoietic colonies was verified by Southern blot. Expression of the neor gene was shown by RNA spot blot. These data demonstrate efficient transfer and expression of the neor gene in both K562 cells and primary human hemopoietic cells from normal and leukemic individuals.
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PMID:Gene transfer to primary normal and malignant human hemopoietic progenitors using recombinant retroviruses. 346 98

A solid-phase, one-step radioimmunoassay was developed for the determination of plasma lactoferrin concentration. The detection limit of the assay is 150 micrograms/l. Leakage of cellular lactoferrin was minimal when EDTA was used as anticoagulant, while results obtained from serum and from heparinized plasma were not reproducible. The plasma lactoferrin concentration of 35 female and 44 male healthy adults was measured in order to determine normal values. The geometric mean of lactoferrin levels in men is about 10% higher than in women: 483 (200-1500) micrograms/l in men and 446 (200-870) micrograms/l in women. Patients with acute and chronic leukaemias were also studied. In 38 patients with chronic myeloid leukaemia plasma lactoferrin levels were increased by three times while the neutrophil count was ten times higher than normal. Normal lactoferrin concentrations were measured in plasma samples from 15 patients with chronic lymphocytic leukaemia in incomplete remission while no detectable lactoferrin was found in samples from those in relapse (10 patients). In the untreated patients or those in relapse (19 cases) of both acute lymphocytic and myeloid leukaemias, plasma lactoferrin concentrations were undetectable while they seemed to return to normal during remission (3 cases). The data obtained indicate that the determination of plasma lactoferrin concentration might play an important role in facilitating the assessment of total blood granulocyte pool (TBGP).
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PMID:Plasma lactoferrin levels in leukaemias. 347 35

Lactoferrin is a major constituent of polymorphonuclear leukocyte granules and is present in mature neutrophils but not in blasts or promyelocytes. We have isolated a cDNA probe for lactoferrin and used it to study the synthesis of lactoferrin mRNA by normal and leukemic granulocyte precursors. The probe pHL-41 has been subcloned in phage m13 and characterized by restriction endonuclease analysis and nucleic acid sequencing. pHL-41 contains approximately 40% of the coding sequence of the lactoferrin gene. The 3' untranslated region includes a stop codon and a possible polyadenylation signal. There is a greater than 98% agreement between the cDNA-deduced amino acid sequence and that determined by analysis of the protein. Myeloid cells from normal bone marrow and circulating leukocytes from patients with chronic granulocytic leukemia contain lactoferrin mRNA transcripts that are indistinguishable in size and relative quantity. The human promyelocytic leukemia cell line HL-60 contains no lactoferrin mRNA. Induction of monocytic or granulocytic differentiation fails to induce the synthesis of detectable lactoferrin message. Similarly, studies with the human myeloblastic leukemia cell line PLB-985 reveal the inability of these cells to produce lactoferrin mRNA even under conditions that bring about morphologically demonstrable granulocytic differentiation. These data suggest that granulocytic differentiation in the leukemic cell lines is incomplete or defective. The presence of lactoferrin may play a role in the orderly expression of the genetic program leading to the development of the normal mature granulocyte.
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PMID:Isolation of lactoferrin cDNA from a human myeloid library and expression of mRNA during normal and leukemic myelopoiesis. 347

Children with Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) have a poorer prognosis than do most pediatric patients with ALL. Because of this poor prognosis and the presence of the Ph chromosome, we have asked whether or not Ph + ALL involves a multipotential stem cell. We cultured hematopoietic progenitors from two children with Ph+ ALL and examined individual BFU-E and CFU-GM colonies for the Ph chromosome. We studied cells from two patients after 18 to 34 months of first complete clinical remission; direct cytogenetic analyses showed 26% and 13% Ph+ metaphases in these patients' marrow cells. BFU-E colonies were obtained from light density marrow cells cultured in methylcellulose supplemented with erythropoietin and CFU-GM colonies from agar or methylcellulose cultures stimulated with leukocyte feeder layers. Fifty-seven G-banded metaphases were recovered from 33 colonies. Ten metaphases from seven colonies were Ph+. Ph+ metaphases were found in three of 12 and three of five BFU-E colonies from the two patients. One of 16 CFU-GM colonies from one patient had the Ph+ chromosome; analyzable metaphases were not obtained from CFU-GM of the other patient. No colonies contained both Ph+ and Ph- cells. These results indicate that Ph+ ALL with persistence of Ph+ cells in remission involves a multipotential stem cell for erythroid and granulocyte/macrophage as well as lymphoid lineages. Multipotential stem cell involvement in the pathogenesis of some childhood Ph+ ALL suggests similarities to Ph+ chronic myelocytic leukemia and may contribute to the poor prognosis of these patients.
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PMID:Evidence for a multipotential stem cell disease in some childhood Philadelphia chromosome-positive acute lymphoblastic leukemia. 347

An IgM class monoclonal antibody Bsp-1 that selectively reacts with human basophils was used to label basophils in normal and leukaemic haemopoietic samples. The immunophenotype of Bsp-1+ basophils was determined using a panel of 21 IgG subclass monoclonal antibodies in two-colour immunofluorescence assays. Basophils expressed the leucocyte common antigen, HLA-ABC antigens and antigens defined by CD11 and CD13 monoclonal antibodies. Other myeloid cell (granulocyte-monocyte) associated anti-antigens, lymphoid cell surface determinants and HLA-DR antigens were not detected. Basophil preparations of 95-98% purity were obtained from the peripheral blood of patients with CML and umbilical cords using fluorescence activated cell sorting techniques. Purified basophils exhibited metachromatic staining with toluidine blue, alcain blue and astra blue. PAS staining was observed in 7% of cord Bsp-1+ cells and of 55% CML Bsp-1+ cells. Between 5% and 10% of basophils were chloroacetate esterase-positive which suggests that some Bsp-1+ cells are immature basophils.
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PMID:The purification of human basophils: their immunophenotype and cytochemistry. 347 96


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