Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early studies examining the effects of purified or recombinant granulocyte colony-stimulating factor (G-CSF) on human leukemia cell lines demonstrated that some cell lines, such as HL-60, could be induced to differentiate in response to G-CSF. In two recent studies reporting the cloning of the human G-CSF receptor (hGCSFR), four classes of receptor cDNA were identified and, surprisingly, the message for this receptor was reportedly expressed by HL-60 at either very low levels or not at all. Using a mouse G-CSF receptor probe, we cloned and sequenced a cDNA for hGCSFR from an HL-60 cDNA library in plasmid and used it to identify 31 additional clones from an HL-60 cDNA library in phage. Polymerase chain reaction analysis of the 31 phage clones established that 29 were derived from class I hGCSFR mRNA, one was derived from class III mRNA, and one was derived from class IV mRNA. In addition, the hGCSFR gene was chromosomally localized by Southern blot analysis of its segregation pattern in a panel of rodent-human hybrid DNAs using the radiolabeled cDNA probe. The hGCSFR locus was present in hybrids retaining the distal short arm of human chromosome 1 and absent in hybrids that did not retain this region. Chromosomal in situ hybridization refined the localization of the hGCSFR gene to region 1p32-p34. The combination of hybrid DNA analysis and in situ hybridization places the hGCSFR gene telomeric to the CSF1, JUN, and TCL-5 loci.
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PMID:Molecular cloning of cDNAs for the human granulocyte colony-stimulating factor receptor from HL-60 and mapping of the gene to chromosome region 1p32-34. 137 13

The p34tax protein [p38tax, p34, p38(XBL), XBL-I] of bovine leukaemia virus (BLV) activates transcription from the BLV long terminal repeat (LTR) promoter. To analyse the functional properties of this protein, inframe insertions and internal deletions were systematically introduced in a plasmid-encoded copy of the p34tax gene. The abilities of wild-type and mutant genes to activate gene expression from the LTR promoter linked to the chloramphenicol acetyltransferase gene and to inhibit trans-activation by the wild-type protein were studied. The trans-activating activity of 14 of the 18 mutants tested was completely abolished, but four mutants each containing a lesion in the internal portion of the polypeptide retained activity. Taken together, these results suggest the presence of an internal region of the polypeptide where structural integrity is less strictly required for the functional activity of this protein. Among the mutants incompetent in the transactivation assay, only two with mutations in the N-terminal region of the polypeptide inhibited transactivation by the wild-type protein in a dose-dependent manner. These results facilitate understanding of the physiological function of the tax protein family.
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PMID:Construction and functional characterization of mutants of the bovine leukaemia virus trans-activator protein p34tax. 165 59

Normal and aberrant immune receptor gene assembly each produce site-specific DNA rearrangements in leukemic lymphoblasts. In either case, these rearrangements provide useful clonal markers for the leukemias in question. In the t(1;14)(p34;q11) translocation associated with T cell acute lymphoblastic leukemia (T-ALL), the breakpoints on chromosome 1 interrupt the tal-1 gene. A site-specific deletion interrupts the same gene in an additional 26% of T-ALL. Thus, nearly one-third of these leukemias contain clustered rearrangements of the tal-1 locus. To test whether these rearrangements can serve as markers for residual disease, we monitored four patients with T-ALL; three of the leukemias contained a deleted (tald) and one a translocated (talt) tal-1 allele. These alleles were recognized by a sensitive amplification/hybridization assay. tald alleles were found in the blood of one patient during the 4th mo of treatment but not thereafter. Using a quantitative assay to measure the fraction of tald alleles in DNA extracts, we estimated that this month 4 sample contained 150 tald copies per 10(6) genome copies. The patient with t(1;14)(p34;q11) (talt) leukemia developed a positive assay during the 20th mo of treatment. By standard criteria, all four patients remain in complete remission 11-20 mo into treatment. We conclude that tal-1 rearrangements provide useful clonal markers for approximately 30% of T-ALLs.
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PMID:Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia. 204 Jun 93

A novel surface membrane nonglycosylated acidic polypeptide (34 kDa), encoded by a structural gene on chromosome 11, has been identified using murine monoclonal antibody (MoAb) 53.6 (IgG2a). MoAb 53.6, raised against uninduced cells of a human erythroleukemia line (HEL), recognizes a surface membrane antigen that is displayed on proliferating (cell cycle phase G1, S, and M + G2 phase) human leukocytes. The expression and redistribution (i.e., patching and capping) of the p34 kDa antigen on 27 different long-term human hematopoietic cell (HHC) lines was defined by fluorescence microscopy. These lines had been established from patients with leukemia or healthy donors and included phenotypically defined populations of T cells, B cells, and myelomonocytic cells. Almost all (greater than 95%) of the leukocytes of the 27 lines reacted strongly with MoAb 53.6. The majority of the leukocytes displayed p34 kDa antigen patching (26/27 lines; patched cells, 96-100%); moreover, 20 of 27 lines exhibited p34 kDa antigen capping (capped cells, 8-96%). Presentation of the p34 kDa antigen on surface membrane ultrastructures, imaged with immunogold using an indirect antibody labeling procedure, was illustrated by scanning electron microscopy, and endocytosis of the gold-tagged antigen-antibody complex was studied by transmission electron microscopy. The HHC lines are thought to represent immortalized populations of different human leukocyte subsets that are in different stages of maturation and/or differentiation; thus these lines should prove useful as models for further characterizing this unique p34 kDa proliferation-associated antigen and for defining the mechanisms and significance of surface membrane antigen redistribution and modulation that has been associated with leukocyte activation and propagation.
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PMID:Expression and capping of a proliferation-associated surface membrane p34 kDa antigen on different human hematopoietic cell lines. 207 35

We report the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;14)(p34;q11) in children with acute lymphoblastic leukemia (ALL). This chromosomal abnormality occurred in leukemia cells from 5 of 1,630 (0.3%) consecutive children with newly diagnosed ALL who were entered on a single Pediatric Oncology Group classification study (POG 8600) between January 1986 and February 1989. The frequency of the t(1;14) was 3% (5 of 168 cases) in children with T-cell ALL. All five cases had pseudodiploid karyotypes, and in 3 cases the t(1;14) was accompanied by a deletion of the long arm of chromosome 6. This translocation is of special interest because the breakpoint on chromosome 14 in band q11 corresponds to the assigned locus of the T-cell receptor alpha/delta chain gene. All five of our patients and three cases reported previously have had T-cell ALL. These findings, considered together, suggest that this translocation is specific for T-cell ALL and that a gene in the 1p34 region may play an important role in malignant transformation of thymocytes.
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PMID:The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. 240 Aug 10

DA6.231 and DA6.164 are mouse monoclonal antibodies that immunoprecipitate HLA-DR-like p34,29 glycoprotein dimers from surface- and metabolically-labeled cells. On lymphoblastoid cell lines the distribution of the 231 epitope is completely nonpolymorphic, while the 164 epitope is present on all cells except on those that are DR7 homozygous. Binding-inhibition studies show that the 231 and 164 epitopes are spatially close to each other when present on the same molecule. The mutual inhibition pattern and the absence of the 164 epitope from the 231+ cells of a few leukemia patients suggest, however, that 231 and 164 epitopes are not invariably present together. Most DR-positive cells possess 231+ and 164+ and 231+ 164- class II molecules in approximately a 2:1 ratio. This has been confirmed by immune depletion studies. Thus DA6.231 appears to define a supralocus epitope. The 164 epitope may be a marker for a subset of class II molecules exhibiting differential expression on various cell types immortalized by malignant transformation.
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PMID:Human MHC class II molecules as differentiation markers. 698 12

We have carried out chromosome analysis in a series of 16 non-Hodgkin Lymphoma (NHL) cases in leukemic phase. The diagnoses in these patients based on histology and immunologic markers were as follows: follicular lymphoma (FL), 3 cases; mantle cell lymphoma (Mc), 4 cases; lymphoplasmacytic lymphoma (LPL), 8 cases, and large cell lymphoma, 1 case. We have shown that the t(14;18), t(11;14), and trisomy 12 retained their subtype association with FL, Mc, and LPL, respectively, as in their nonleukemic counterparts with one case of FL showing t(1;19)(q23;p13). Among the four LPL cases without trisomy 12, one case each showed t(12;14)(q13;q32), trisomy 14, t(1;3)(p34;q21), and del(3)(q21). The t(1;19) and t(12;14) may represent rare events in FL and LPL, respectively, and may be uniquely associated with the leukemic phase. The breakpoint 14q32 was the most common single breakpoint involved, sometimes involving both chromosome 14 homologues depicting its association with primary and secondary genetic events in the disease progression. In addition to the main abnormalities, we have shown additional complex abnormalities in 14 of 16 cases. Among these, chromosome 3 was the most commonly involved, affecting the short or long arm or the whole chromosome; 5 of the 16 cases involved breakpoint 3q21. The high incidence of additional abnormalities in these NHL in leukemic phase suggest an association with the development of leukemia and progression of the disease.
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PMID:Cytogenetic abnormalities in the leukemic phase of non-Hodgkin lymphoma. 765 98

Intracellular p34cdc2 appears to be responsible for excessive cell growth. Therefore, disturbance of this cell cycle kinase by a specific monoclonal IgG1 anti-cdc2 antibody that specifically recognizes the product of the cdc2 gene, p34, was attempted. By using the surface p34 positive and rapidly proliferating HL-60 human promyelocytic leukemia cell line, transmission electron microscopy (TEM) and other standard techniques, it was found that the antibody, after an initial outer membrane attachment at 4 degrees C and entering the cells by raising the temperature to 37 degrees C, is directed and bound specifically on to the cell's nucleolus. This binding does not only demonstrate the intracellular localization of cdc2, but also appears to disturb its function. It thus induces a class II (HLA-DR) enhancement, increases the phagocytic ability of the cells and causes cellular elongation marked by a non-permanent adherence pattern. The results obtained are IgG independent and indicate that disturbance of constitutive cdc2 expression drives the cells to another level of maturation. The mechanisms behind these actions are still unknown. The results, however, may indicate that the regulatory pathways that govern the functioning of cell cycle stages are actively involved in the processes of cell differentiation. Similar findings have also been released where terminal murine erythro-differentiation may be achieved by manipulation of specific cell cycle kinases. On the contrary, normal already differentiated cdc2 negative human blood-derived monocytes remain insensitive to anti-cdc2 treatment, supporting the view that the presence of this kinase may be one of the reasons leading malignant cells to excessive growth, and that laboratory manipulation and reinfusion of these cells to leukemia patients may be a possible regimen for AML.
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PMID:Specific nuclear binding of anti-cdc2 on p34cdc2 positive autonomously grown human leukemia cells induces differentiation. 765 99

We have cloned and characterized a novel gene at the site of a t(1;3)(p34;p21) translocation breakpoint in T-cell acute lymphoblastic leukemia. A cDNA for this gene, for which we propose the designation TCTA (T-cell leukemia translocation-associated gene), has been cloned. TCTA mRNA is expressed ubiquitously in normal tissues, with the highest levels of expression seen in the kidney. The TCTA gene is conserved throughout evolution in organisms ranging from Drosophila to humans. A short open reading frame encodes a predicted M(r) 12,000 protein without strong homology to any previously reported proteins. Of note, genomic Southern blots demonstrated a reduced TCTA signal in three of four small cell lung cancer cell lines tested, suggesting loss of one of the two copies of the gene.
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PMID:Cloning and characterization of TCTA, a gene located at the site of a t(1;3) translocation. 772 59

A novel and as yet unrecorded translocation, (1;2)(p34;p21-22), detected in a patient with acute myeloid leukemia (AML) is reported. The leukemia--in this case, AML-M4--showed a rapidly progressive fatal course despite an early transient response to aggressive chemotherapy. In this patient, the leukemic cells showed a novel balanced translocation, (1;2)(p34;p21-22), in most of the metaphases at the time of diagnosis and during subsequent relapse. Interferon-inducible double-stranded RNA-dependent protein kinase (ds RNA-PK) is located in the chromosome region, 2p21-22, that was involved in the translocation in this case. The possible role of ds RNA-PK in leukemogenesis is briefly mentioned.
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PMID:A novel translocation (1;2)(p34;p21-22) in acute myelomonoblastic leukemia. 977 15


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