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)

The osmotic behavior of control lymphocytes (CL) and polymorphonuclears (CPMN) was compared with that of cells from patients with chronic lymphocytic leukemia (CLL) and chronic myelocytic leukemia (CML), using the method of gradual dialysis against distilled water. The results were evaluated with a fragiligraph, and by scanning (SEM) and transmission (TEM) electron microscopy. The fragiligraphy curves showed that CLL cells are more resistant to osmotic pressure than the CL, whereas the curves for CPMN and CML cells showed an overlap. Surface alterations in CL appeared as early as 1 min of dialysis, while in CLL cells the membrane did not show major alterations even after 5 min of dialysis. CPMN also showed alterations earlier than CML cells, but this difference was not as prominent as in the case of lymphocytes and was observed for a maximum of 3 min of dialysis. The internal structure of the cells was altered earlier than the surface membrane and this was expressed mainly in the nucleus in both control and leukemic cells. Also in this respect, the internal structure of CL was altered earlier than that of CLL cells, whereas no major differences were observed between CPMN and CML cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1982
PMID:SEM and TEM studies on the osmotic behavior of control and leukemic lymphocytes and polymorphonuclears. 612 53

Chloramphenicol resistance (Cmlr) of Streptomyces coelicolor A3(2) behaves like a transposon locus, not being localisable in any region of the map and yet being transferable in crosses at a rate comparable to that of chromosomal markers. It can also be transposed onto a plasmid (SCP1) and back to the chromosome. Some traits, such as arginino-succinate synthase production (ArgG), aerial mycelium formation (AmyA), resistance to tetracycline and to rifamycin C appear to be joined to Cml in three processes: co-mutation, i.e. simultaneous loss, post-mutation, i.e. spontaneous loss at high frequency in subclones from Cmls strains, co-transfer, i.e. joint transfer with the cml locus in crosses or during infection by the aggregate SCP1::SCTn1 plasmid. All these processes have been consistently observed with special attention to the argG locus.
Mol Gen Genet 1983
PMID:Properties of transposon SCTn1 of Streptomyces coelicolor A3(2). 631 Mar 49

Somatic cell hybrids containing chromosomes from a patient with chronic myeloid leukaemia were used as a source of DNA for filter hybridizations with immunoglobulin lambda light chain constant region and c-onc probes. The results show that at least part of the human lambda constant region locus remains on the abnormal chromosome 22 (the Philadelphia chromosome) and therefore that this translocation occurs distal to these genes. Further, in the patient studied the c-abl gene has been translocated to the abnormal chromosome 22, thus creating a new genetic linkage between C lambda and c-abl genes.
Mol Biol Med 1983 Jul
PMID:The breakpoint of the Philadelphia chromosome 22 in chronic myeloid leukaemia is distal to the immunoglobulin lambda light chain constant region genes. 643 36

We have investigated the configuration of immunoglobulin (Ig) genes in leukaemic cells in 17 patients with B-cell leukaemias (11 chronic lymphocytic leukaemias (B-CLL); 4 prolymphocytic leukaemias (B-PLL), and two hairy cell leukaemias (HCL)). In addition we studied four patients with T chronic lymphocytic leukaemia (T-CLL); four patients with acute leukaemia (3 acute lymphoblastic leukaemias (ALL), and 1 mixed acute leukaemia (M.AL)); and six patients with chronic granulocytic leukaemias in blastic crisis (CGL.BC). The heavy chain genes (H) were analysed by using probes for the constant region of the mu chains (C mu) and for the joining region (JH). The light chain genes were analysed by using probes for the constant region of the kappa (C kappa) and lambda (C lambda) chains. We have found rearranged Ig genes in all cases of B-CLL, B-PLL and HCL, but in none of the patients with T-CLL. In one case of HCL, both mu genes were deleted, indicating that in this case the class switch has taken place. In four out of six cases with either ALL or lymphoid CGL.BC and in one case of M.AL, an Ig gene rearrangement was also found. No rearrangement was detected in two cases of myeloid CGL.BC. When the combination of rearrangement versus germ-line configuration was considered, a variety of patterns emerge, but in no case did we find a L chain gene rearranged without at least one H chain gene being rearranged as well. Whereas in the majority of cases of B-CLL only one H chain gene is rearranged, in nearly all cases of B-PLL both H chain genes are rearranged. By systematic analysis of restriction fragment sizes of rearranged genes, we have established that a large number of different variable regions for the H chain (VH) are involved in Ig gene rearrangement in B-cell malignancies. Our data confirm that testing for Ig gene rearrangement may be the most sensitive and specific test for identifying leukaemic cells of B lineage.
Mol Biol Med 1984 Feb
PMID:DNA rearrangements of immunoglobulin genes correlate with phenotypic markers in B-cell malignancies. 643 75

The phage 11 of R. meliloti performs generalized transduction. This was confirmed by the variety of single markers transferred and by separating transducing particles containing BUdR-labelled bacterial DNA. The transduction frequencies depended on the marker. Linked alleles were mapped by cotransduction on fragments of bacterial DNA equal in size to the phage DNA. With crosses between antibiotic resistancy and auxotrophic markers a partial map was constructed with str, cml, pur-19, and leu-44 sites. With a few multi-auxotrophic mutants linkage data of conjugation were compared with the linkage by cotransduction.
Mol Gen Genet 1980
PMID:Generalized transduction in Rhizobium meliloti. 693 May 36

Perlecan is a modular heparan sulfate proteoglycan that harbors five domains with homology to the low density lipoprotein receptor, epidermal growth factor, laminin and neural cell adhesion molecule. Using a monoclonal antibody directed against the laminin-like domain of perlecan, we have recently shown that perlecan is widely expressed in all lymphoreticular systems. To investigate further this observation we have studied the expression of perlecan in two human leukemic cell lines. Using reverse transcriptase-PCR, ribonuclease protection assay, and metabolic labeling we detected significant perlecan expression in the multipotential cell line K562, originally derived from a patient with chronic myelogenous leukemia. In contrast, the promyelocytic cell line HL-60 expressed perlecan at barely detectable levels. These results were intriguing because the K562 cells do not assemble or produce a classical basement membrane. Following induction with either sodium butyrate or the phorbol diester 12-0-tetradecanoylphorbol-13-acetate (TPA), K562 and HL-60 differentiate into early progenitor cells with erythroid or megakaryocytic properties, respectively. Following treatment of K562 and HL-60 cells with either of these agents, perlecan expression was markedly increased in K562 cells. In contrast, we could detect perlecan protein synthesis in HL-60 cells only at very low levels, even after induction with TPA or sodium butyrate. Collectively, these results indicate that perlecan is actively synthesized by bone marrow derived cells and suggest that this proteoglycan may play a role in hematopoietic cell differentiation.
Mol Cell Biochem 1995 Apr 12
PMID:The proteoglycan perlecan is expressed in the erythroleukemia cell line K562 and is upregulated by sodium butyrate and phorbol ester. 754 67

BCR-ABL is a deregulated tyrosine kinase expressed in Philadelphia chromosome-positive human leukemias. Prolongation of hematopoietic cell survival by inhibition of apoptosis has been proposed to be an integral component of BCR-ABL-induced chronic myelogenous leukemia. BCR-ABL elicits transformation of both fibroblast and hematopoietic cells and blocks apoptosis following cytokine deprivation in various factor-dependent cells. To elucidate the mechanisms whereby BCR-ABL induces transformation and blocks apoptosis in hematopoietic cells, we examined the biological effects of expression of a series of BCR-ABL mutants. Single amino acid substitutions in the GRB2 binding site (Y177F), Src homology 2 domain (R552L), or an autophosphorylation site in the tyrosine kinase domain (Y793F) do not diminish the antiapoptotic and transforming properties of BCR-ABL in hematopoietic cells, although these mutations were previously shown to drastically reduce the transforming activity of BCR-ABL in fibroblasts. A BCR-ABL molecule containing all three mutations (Y177F/R552L/Y793F) exhibits a severe decrease in transforming and antiapoptotic activities compared with the wild-type BCR-ABL protein in 32D myeloid progenitor cells. Ras is activated, the SHC adapter protein is tyrosine phosphorylated and binds GRB2, and myc mRNA levels are increased following expression of all kinase active BCR-ABL proteins with the exception of the Y177F/R552L/Y793F BCR-ABL mutant in 32D cells. We propose that BCR-ABL uses multiple pathways to activate Ras in hematopoietic cells and that this activation is necessary for the transforming and antiapoptotic activities of BCR-ABL. However, Ras activation is not sufficient for BCR-ABL-mediated transformation. A BCR-ABL deletion mutant (delta 176-427) that activates Ras and blocks apoptosis but has severely impaired transforming ability in 32D cells has been identified. These data suggest that BCR-ABL requires additional signaling components to elicit tumorigenic growth which are distinct from those required to block apoptosis.
Mol Cell Biol 1995 Oct
PMID:Structural and signaling requirements for BCR-ABL-mediated transformation and inhibition of apoptosis. 756 5

Lectin-receptors on leukocyte and endothelial surfaces are becoming more important in the light of increasing evidence which implicates lectin-carbohydrate interactions in diverse physiological phenomena. This study reports the identification of a major 118 kDa granulocyte surface protein, (Protein 1 a) which binds the lectin wheat germ agglutinin (WGA), and is distinctly different from reported WGA binding granulocyte membrane proteins. Protein 1 a has been isolated from the Triton-soluble and Triton-insoluble lysates of normal individuals and patients with Chronic Myeloid Leukemia (CML) using a combination of differential solubilization, lectin affinity, ion exchange chromatography and HPLC. The protein from the detergent lysates of both normal and CML granulocytes has similar pI values, lectin affinities, and hydrophobicity. However, its solubility in Triton is different in the two cell types. In 71% of CML cases examined, Protein 1 a exhibits decreased Triton solubility suggesting its increased association with the cytoskeleton (CSK). Stimulation of normal granulocytes with WGA leads to the translocation of the soluble form of Protein 1 a to the Triton-insoluble fraction. This cytoskeletal recruitment of Protein 1 a is sustained only under conditions of excess WGA and occupied receptor. The CSK disruptive agent dihydrocytochalasin B (H2CB) releases the insoluble form of the receptor into the Triton-soluble fraction. Investigation of a CSK-involving process such as ligand internalization revealed that CML granulocytes exhibit slower kinetics of internalization of fluorescent WGA molecules.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1995 Mar 23
PMID:Protein 1a: a major wheat germ agglutinin binding protein on the surface of human granulocytes associated with the cytoskeleton. 762 87

Constitutive activation of the Abelson (Abl) protein tyrosine kinase (PTK) is a causative event in chronic myeloid leukemia, where intense chemotherapy currently fails to eradicate the leukemic clone. Using a mouse mast cell line (IC.DP), we previously showed that v-Abl PTK induced resistance to the anti-cancer drugs melphalan and hydroxyurea by the suppression of apoptosis. Here, using this cell line, we demonstrate by alkaline elution that v-Abl PTK did not affect the levels of DNA damage induced by either drug. This confirms that v-Abl PTK acts downstream of the drug-target interaction to prevent the coupling of drug-induced damage to the apoptotic pathway. Although Abl PTK- and interleukin-3 (IL-3)-stimulated signaling events share common signaling pathways, a similar level of drug resistance was not provided by IL-3, implying that Abl PTK does not merely mimic an IL-3 survival signaling pathway. Previously we demonstrated translocation of protein kinase C-beta II stimulated by activation of Abl PTK. Drug sensitivity was restored in cells with active v-Abl PTK by simultaneous addition of calphostin C, an inhibitor of protein kinase C, suggesting a role for protein kinase C in the suppression of drug-induced apoptosis by v-Abl PTK. One novel strategy for the treatment of chronic myeloid leukemia could therefore include the use of a downstream modifier of the Abl PTK-mediated survival signaling pathway to render leukemic cells more sensitive to a second drug, such as a cytotoxic agent.
Mol Pharmacol 1995 Aug
PMID:Characterization of drug resistance mediated via the suppression of apoptosis by Abelson protein tyrosine kinase. 765 67

Proliferation of normal cells in a multicellular organism requires not only growth factors but also the proper attachment to the extracellular matrix. A hallmark of neoplastic transformation is the loss of anchorage dependence which usually accompanies the loss of growth factor requirement. The Bcr-Abl tyrosine kinase of human leukemias is shown here to abrogate only the anchorage, not the growth factor, requirement. Bcr-Abl-transformed cells grow in soft agar but do not proliferate in serum-free media. Bcr-Abl does not activate the mitogenic pathway, as indicated by its inability to induce enhancers such as the serum response element or the tetradecanoyl phorbol acetate response element (TRE). However, Bcr-Abl can alleviate the anchorage requirement for the induction of the TRE enhancer; i.e., it allows serum to activate the TRE in detached cells. This activity is dependent on the association of an active Bcr-Abl tyrosine kinase with the actin filaments. Despite its association with the adapter protein Grb2, Bcr-Abl's effect on the TRE enhancer is not blocked by dominant negative Ras or Raf. The finding that Bcr-Abl tyrosine kinase abrogates only anchorage dependence may have important implications on the pathogenesis of chronic myelogenous leukemia.
Mol Cell Biol 1995 Mar
PMID:The human leukemia oncogene bcr-abl abrogates the anchorage requirement but not the growth factor requirement for proliferation. 786 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>