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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In acute lymphoblastic leukemia (ALL) diagnostic samples and cell lines with unequivocal B cell precursor (common) or T cell precursor immunophenotypes, there is inappropriate or cross-lineage IgH or T cell receptor beta gene (TCR beta) rearrangement in approximately 25% of the cases. The frequency of such rearrangements is lower in mature lymphoid neoplasms and acute myeloblastic leukemia. The most immature B lineage ALL ('null' ALL) has a much lower frequency of TCR gene rearrangement than the common variant of B cell precursor ALL and also has a high frequency of oligoclonal rearrangements of IgH genes. Non-T leukemic cells with inappropriately rearranged TCR beta gene did not necessarily have a rearranged TCR gamma gene. Inappropriately rearranged IgH or TCR genes are usually not expressed at the mRNA level, and the gene for the TCR associated protein T3 delta is not detectably expressed at the mRNA or protein level in leukemias classified unambiguously as non-T. Five cases of acute leukemia with ambiguous or mixed lineage immunophenotypes (myeloid + T or myeloid + B) are described. These five had diverse patterns of IgH, TCR beta, and TCR gamma rearrangement, and all expressed terminal transferase concomitantly with MY9 (CD33). The T3 delta gene was expressed in two cases, which also expressed other T cell markers indicating that coordinated lymphoid lineage programs had been initiated. The implications of these observations for lineage-associated regulation of genes during normal differentiation and leukemogenesis are discussed.
Leukemia 1987 Sep
PMID:Lineage specificity of rearrangement and expression of genes encoding the T cell receptor-T3 complex and immunoglobulin heavy chain in leukemia. 311 13

Activation of the cellular oncogene c-N-ras has been frequently observed in DNA from leukemic cells in acute myeloid leukemia (AML). Ras gene activation sufficient to mediate in vitro transformation and rodent tumorigenesis usually results from point mutations and amino acid substitutions in the 12th or 61st codons. In AML and the related myelodysplastic syndromes, amino acid substitution at the 13th codon has been observed. An activated c-N-ras gene from a 45-year-old patient with AML was isolated by transfection analysis and subjected to molecular cloning and sequence analysis. A point mutation of the 12th codon (GGT to GAT) resulting in aspartic acid substitution for glycine was observed. In other neoplasms such as colon cancer, specific ras mutations occur predominantly (e.g., K-ras, codon 12). This predominance has been of demonstrable value in analyzing large cohorts for ras activation with techniques that are rapid and economical, such as oligonucleotide hybridization. It had previously been thought that such a predominance for activation of c-N-ras at codon 13 existed in AML; however, this study in concert with others underscores the importance of 12th codon c-N-ras mutations, along with 13th and 61st codon mutations in the molecular pathogenesis of AML. Guanylate to adenylate transition mutations are commonly observed in AML and may provide insight into potential environmental leukemogens. Addressing all commonly prevalent ras activating mutations bears impact in the future design of molecular surveys of the role of ras activation in leukemogenesis.
Leukemia 1988 Feb
PMID:12th codon mutation resulting in c-N-ras activation in acute myelogenous leukemia. 327 72

Studies of the relationships between ionizing radiation, bone marrow transplantation and leukemogenesis were carried out in 343 LACA mice. The recipients (female) were given whole-body irradiation with 7 or 8 Gy of Co-60 gamma-rays, while the donors (male) were given whole-body irradiation with 3, 1.5, 0.5, 0.1, 0.05 and 0 Gy of Co-60 gamma-rays. Each recipient was intravenously infused with 1-3 X 10(7) of the mixed marrow cells of donors. In the result, the average incidence of surviving over 1 month was 86% in the recipients. Myelocytic leukemia developed in all the transplanted groups, the average incidence being 88.5%. Leukemia was observed in 1.5-2.5 months after transplantation in the recipients receiving marrow cells from donors exposed to 3 Gy, but in 5-8 months in other groups. It was demonstrated by the analysis of Y-chromosome that the leukemic cells were derived from the donor's marrow cells. The results suggest that marrow transplantation for the mice irradiated by Co-60 gamma-rays of lethal dose can protect them from death, but promote the development of leukemia. Radiation can induce production of factors which lead to leukemic transformation of engrafted normal marrow cells in the irradiated mice; the direct damage of DNA caused by radiation is not the unique factor that gives rise to leukemia.
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PMID:Relationships between ionizing radiation, bone marrow transplantation and leukemogenesis. 330 25

Leukemia was observed in 45 per cent of hairless mice at 8 to 10 months of age and 72 per cent at 18 months. The incidence of leukemia in normal heterozygous mice of the same age is about one per cent at 10 months and increases to 20 per cent at 18 months. Other tumors are rare; two mammary adenocarcinomas occurred in heterozygotes, and an epidermal squamous cell carcinoma was found in a hairless mouse. Murine leukemia virus was isolated from normal and leukemic mice of both genotypes on SWR/J- and C57L/J-METC, but not BALB/cJ-METC. If this virus is responsible for the leukemia in HRS/J mice, the mutant gene (hr) enhances susceptibility and the wild-type allele (+) induces resistance to leukemogenesis, i.e., malignant transformation of reticulo-endothelial tissues occurs rather than inhibition of viral replication as both genotypes harbor virus in high titers. The two types of HRS/J mice, hr/hr and hr/+, are congenic, i.e., they differ only with respect to one allele (hr or +) at the mutant locus. This single gene difference should lend itself to analysis of the interaction of a specific gene and murine leukemia virus.
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PMID:Genetic control by the hr-locus of susceptibility and resistance to leukemia. 431 May 15

A survey of age-related expression of thymus-leukemia (TL) alloantigens (TL 1,2,4) among bone marrow, spleen and thymus cells of grossly normal and leukemic AKR/J mice is presented. The response of the stained cells to antisera directed against TL antigens was analysed by means of the fluorescence-activated cell sorter (FACS) apparatus. A transient expression of TL antigens on cells among the bone marrow population was observed in 1- to 20-day-old AKR/J mice, followed by an undetectable level up to 3 months and its reappearance thereafter. Thymocytes expressed TL from the age of 4 months onwards, reaching a transient maximal level at the age of 6 months in females and 8 months in males. Subsequently, an age-related decrease took place. In spleen cells from newborn mice TL expression was seen, followed by a rapid decrease to undetectable levels up to the age of 5-6 months. In most tests the expression of TL4 preceded the TL 1,2 phenotype. The frequency of TL+ leukemias was about 50% among the early-occurring spontaneous leukemias (in 5- to 7-month-old mice) and decreased to 20% with age increase. Leukemia development following treatment with methyl-nitrosourea (MNUA) or exposure to X-rays increased the frequency of TL+ tumors to 75-100%. These results suggest that heterogeneous target cells are involved in AKR leukemogenesis.
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PMID:Age-related expression of TL antigen in AKR/J mice. 674 14

The effect of hematopoietic stem cell age on leukemogenesis in vitro was tested in nonrecharged, corticosterold-supplemented NIH Swiss [N:NIH(S)] mouse long-term bone marrow cultures infected with Friend murine leukemia virus of anemia-inducing strain (F-MuLV-A) or spleen focus-forming virus (SFFV) [Rauscher murine leukemia virus (R-MuLV)], a pseudotype virus derived by rescue of the SFFV genome from SFFV-Balb/3T3 clone A31 nonproducer cells with clonal helper R-MuLV. Cultures at 33 degrees C derived from 10-day-old or adult mouse marrow generated colony-forming unit culture granulocytic macrophage (CFUc) progenitor cells for over 20 weeks and colony-forming unit spleen cells for 14 weeks and generated permanent granulocytic leukemia cell lines after infection with F-MuLV-A at week 1, 2, or 4 but not at week 8. Leukemia lines were of granulocyte phenotype whether induced by F-MuLV-A or SFFV (R-MuLV) and synthesized myeloperoxidase and lysozyme but were restricted in ability to generate superoxide in response to phorbol myristate acetate stimulation. Cultures (31 degrees C) infected with temperature-sensitive (ts) helper virus mutant pseudotypes of SFFV as well as SFFV (R-MuLV) generated granulocytic leukemia lines, whereas only SFFV (R-MuLV) pseudotype virus-infected cultures became leukemic at 37 degrees C. R-MuLV wild type or ts mutant helper virus infection alone increased cell proliferation and numbers of CFUc but did not generate leukemia. These data indicated that gene(s) specific to F-MuLV-A or a virus rescued from SFFV-Balb/3T3 clone A31 nonproducer cells are required for transformation in vitro of a hematopoietic stem cell present in early but absent in late bone marrow cultures.
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PMID:Virus and cell requirements for Friend virus granulocytic leukemogenesis in long-term bone marrow cultures of NIH swiss [N:NIH(S)] mice. 692 98

Recurrent chromosome translocations involving 11p13 and 14q11 are found in 5-10% of cases of T-ALL. The gene involved in the translocation on chromosome 14 is the T cell antigen receptor alpha or delta. The putative oncogene on chromosome 11 is rhombotin 2 (RBTN2)/translocated in T cell gene 2 (ttg-2), a member of the LIM family of proteins. In this paper we characterize a cell line KOPT-K1 that has a t(11;14)(p13;q11). The breakpoint on chromosome 11 involves an Alu-rich region with the break occurring between two Alu sequences on chromosome 11. In addition, approximately 70 bases from the break on chromosome 11 is a tetranucleotide repeat. Whether either of these structures played a role in the translocation is not known. No heptamer or nonamer sequences, implicated in other rearrangements were found near the breakpoint. The breakpoint on chromosome 11 maps more centromeric than previous translocations of this region. Despite this the RBTN2 gene is highly expressed in KOPT-K1. This cell line will be useful for investigating the role of RBTN2 in leukemogenesis and the mechanism by which the translocation alters the expression of RBTN2.
Leukemia 1995 Nov
PMID:Molecular characterization of a chromosome translocation breakpoint t(11;14)(p13;q11) from the cell line KOPT-K1. 747 67

Trisomy 12 and a deletion of chromosome 13 are the most common chromosome abnormalities in patients with B cell chronic lymphocytic leukemia (B-CLL). We determined the frequencies of these abnormalities in Japanese B-CLL patients by FISH in interphase nuclei. Specimens from 42 patients were analyzed using both DNA probes specific to the centromeric region of chromosome 12 and the retinoblastoma (RB) gene. Among 42 patients, eight had trisomy 12 and 12 had the RB gene deletion. We found aberrations of trisomy 12 and the RB gene deletion in a totally different group of patients. This suggested that the trisomy 12 and the RB gene deletion occur in different clones and the presence of which in the same patient may be rare. Furthermore, the frequency of trisomy 12 (19%) found in Japanese B-CLL was lower than that in Western countries (30-35%). On the contrary, the frequency of the RB gene deletion (28.6%) was almost the same as in European B-CLL (30-35%). These results will be helpful in understanding the leukemogenesis of B-CLL.
Leukemia 1995 Nov
PMID:Independent clones of trisomy 12 and retinoblastoma gene deletion in Japanese B cell chronic lymphocytic leukemia, detected by fluorescence in situ hybridization. 747 69

The human tri-thorax gene (HRX) also called ALL-1 (Acute Lymphocytic Leukemia-1) as well as MLL (Myeloid-lymphoid or Mixed-lineage Leukemia) gene, is disrupted in the majority of leukemias with chromosomal abnormalities involving 11q23. The alteration of the gene is related to leukemogenesis of various types such as acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and acute mixed lineage leukemia. The gene is also rearranged in cases of secondary AML developing after exposure to chemotherapeutic agents, especially topoisomerase II inhibitors. In at least one report, genomic analysis of this recombination site showed the breakpoint to be a topoisomerase II binding site and that exposure to the inhibitor could induce the rearrangement. If exposure induces the rearrangement of the gene, secondary ALL as well as secondary AML could occur after exposure to these agents, because the type of leukemias with rearranged HRX gene is not limited to AML. We present here such a case of secondary ALL with this gene rearrangement which occurred during adjuvant chemotherapy for breast cancer. Although less cases of secondary ALL are reported in comparison with those of secondary AML, such case reports have been accumulating. The incidence of this type of leukemia should be clarified in the future.
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PMID:HRX gene rearrangement in secondary acute lymphoblastic leukemia. 754 29

A basic helix-loop-helix phosphoprotein gene, G0S8, was recently isolated by differential screening of cDNA from human blood mononuclear cells stimulated with a T cell mitogen and cycloheximide. In this study, G0S8 expression was examined in normal and malignant hematopoietic cells by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). G0S8 expression was observed in most fresh samples of acute myelogenous leukemia (AML) (28/30) and most cases of adult acute lymphoblastic leukemia (ALL) (9/11) regardless of clinical classification. G0S8 mRNA was also detected in all cases tested of chronic myelogenous leukemia (CML) in blast crisis. However, G0S8 expression was not detected in CML patients in chronic phase, nor in normal bone marrow or other hematopoietic cells. G0S8 has been mapped using fluorescence in situ hybridization (FISH) to human chromosome 1q31, the same site reported for the B cell homolog BL34/1R20 and within a region implicated in the development of hematological malignancies. The consistent observation of G0S8 mRNA in patient samples of acute leukemia suggests that G0S8 expression may either play a role in leukemogenesis or represent a common consequence of dysregulated growth.
Leukemia 1995 Aug
PMID:Differential expression of a basic helix-loop-helix phosphoprotein gene, G0S8, in acute leukemia and localization to human chromosome 1q31. 764 15


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