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)

The cytokine secreted by a human hybrid B cell line (STS 25) obtained by fusion of the B lymphoblastoid cell line WI-L2-729-HF2 with neoplastic B cells from a patient with B cell non-Hodgkin's lymphoma (B-NHL) was characterized as IL-1 alpha. STS 25 cells express the idiotypic (Id+) immunoglobulin (Ig) specific for the neoplastic B cells of the B-NHL patient. STS 25 cells are weakly positive for surface mu delta kappa and in addition express the surface markers CD19, CD20, CD23, HLA class I and II, and the 4F2 activation antigen. STS 25 cells are also Epstein-Barr nuclear antigen positive but do not secrete viral particles. Serum-free culture supernatant from STS 25 cells (STS 25 SUP) does not show activity in assays for interleukin-2 (IL-2), -4 (IL-4), -6 (IL-6), interferon or tumor necrosis factor, but is active in the thymocyte costimulation assay and the D10.G4.1 T helper clone proliferation assay for interleukin-1 (IL-1). The IL-1 character of the STS 25 SUP activity was confirmed in inhibition studies with three different poly- or monoclonal anti-IL-1 antibodies (31, 88, and 94% inhibition in thymocyte costimulation assay, respectively). Furthermore, complete blocking of D10.G4.1 cell proliferation mediated by STS 25 SUP was observed by including anti-IL-1 alpha specific antibody in the assay, whereas anti-IL-1 beta antibody had no effect. These results indicate that this STS 25 SUP activity can be attributed to the presence of IL-1 alpha in the supernatant. Northern blot analysis of total STS 25 cellular RNA using IL-1 alpha or IL-1 beta specific probes revealed the constitutive expression of IL-1 alpha messenger RNA by STS 25 cells. In contrast, no IL-1 beta message was detectable, not even after treatment of the cells with phorbol ester or cycloheximide, which resulted in approximately 5-fold enhancement of IL-1 alpha mRNA expression. Binding studies with radiolabeled recombinant (r) IL-1 alpha indicated the presence of high numbers of IL-1 receptors on STS 25 cells (1,170 per cell, Kd = 392 pM). Although both IL-1 alpha and IL-1 beta bound to these IL-1 receptors, no indication was found for IL-1 mediated regulation of STS 25 cell growth.(ABSTRACT TRUNCATED AT 400 WORDS)
Leukemia 1989 Aug
PMID:Functional and molecular characterization of B cell line derived interleukin-1 alpha. 278 53

Moloney murine leukemia virus (M-MuLV) induces promonocytic leukemias, called MML, in pristane-treated adult mice. These tumors invariably express fused gag-myb mRNA as a consequence of virus integration and activation of the c-myb locus. In the present study it was determined that while BALB/c and DBA/2N mice are highly susceptible, C57BL/6, C3H/He, STS/A, NFS, NIH/Swiss, SJL/J, and NZB mice are strongly resistant to tumor induction. Although C57BL/6 mice were resistant because they were unable to support early virus replication in hematopoietic tissue, NFS and C3H/He mice supported replication and were shown, using RT-PCR, to have cells in the bone marrow and spleen that expressed the aberrant, leukemia-related gag-myb mRNA. This provided evidence that early stages of leukemia were permitted to develop in these mice, but preneoplastic cells were unable to progress to the acute phase. Experiments in which MML was induced by M-MuLV plus pristane treatment in immunodeficient C3H/He nu/nu and sublethally irradiated C3H/He mice suggested that the immune response may play a role in eliminating preleukemic cells in immunocompetent C3H/He. Tumors from these mice had rearrangements at the c-myb locus and expressed gag-myb RNA. It was concluded that, at least in the case of C3H/He mice, resistance is not due to an inability of virus to activate c-myb or to a lack of other tumor promoting events. Rather, leukemia development appears to be restricted by an immune response, presumably T-cell mediated. Evidence is provided that non-H-2 MHC genes are required for resistance in both C57BL/6 and C3H/He mice and that resistance is dominant. This provides an animal model for the study of tumor progression as it relates to the immune response.
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PMID:Susceptibility and resistance to Moloney murine leukemia virus-induced promonocytic leukemia. 797 49

Positional cloning of the putative gene responsible for transient abnormal myelopoiesis (TAM) and that for multiple cartilaginous exostoses (MEX) is described. TAM is a leukemoid reaction occurring frequently in Down syndrome (DS) newborn infants and they often develop true leukemia several years later. The previous findings of "disomic homozygosity in trisomic cells" and tentative mapping of the TAM gene to 21q11.1, and an encounter of a unique DS-associated TAM patient with inv(21) (q11.1q22.13) let us start positional cloning of the TAM gene. One type of MEX is an autosomal dominant disorder and patients with MEX sometimes develop chondrosarcoma. The MEX gene has been mapped to 8q24. We encountered a sporadic case of MEX with de novo t(8q; 13q). Thus, we hypothesized that in both patients, the TAM and the MEX genes are disrupted by the structural chromosome abnormalities. For TAM, we first mapped the proximal breakpoint of inv(21) between 2 STSs using 7 cosmid clones as FISH probes that were isolated on the basis of STS markers at the 21q11.1 region, isolated their corresponding YACs, and then analyzed them. However, since YACs corresponding to 2 other STSs between the two markers could not be isolated, we carried out a chromosome walking to construct a cosmid contig between the 2 STSs. Southern analysis with a cosmid clone within the contig detected EcoRI-/HindIII extra bands on the patient's DNA. The cDNA screening and exon trapping to isolate a gene from the region are underway. Similarly, in the MEX patient we mapped the 8q breakpoint between 2 cosmid markers, then isolated YACs and cosmid subclones. By exon trapping after detection of a cosmid covering the breakpoint, an exon-like sequence was isolated. The 3'-RACE/5'-RACE revealed a novel transcript from this cosmid. Whether the transcript is the MEX gene remains to be determined.
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PMID:[Positional cloning of the putative gene responsible for transient abnormal myelopoiesis and that for multiple cartilaginous exostoses]. 869 34

Chromosome band 9p21-22 is one of the most common targets for deletions in cancer. The p16 tumor suppressor gene maps to this region and is inactivated in a wide variety of tumor cell lines and primary tumors. However, in some of the neoplasms with frequent 9p21 loss of heterozygosity (LOH), a structurally and functionally normal p16 is found suggesting that this gene might not be the primary or only target for inactivation. To define the smallest region of overlap of deletions at chromosome band 9p21-22 and to clarify the involvement of p16, p15 and the IFN cluster gene in lymphoblastic leukemias, we used a multiplex polymerase chain reaction to construct a detailed map of deletions at 9p21-22. We studied DNA from 30 lymphoblastic leukemia patients and nine cell lines using 10 genes/markers that map to this region, including four STS markers located between p16 and D9S171 (STS1, STS2) or between p16 and IFNalpha (STS3, STS4). We found that the size of the deletions in this region is variable and that the commonly deleted region spans at least 400 kb; it includes the p16 gene but excludes the IFN gene cluster and the p15 gene. The identification of this commonly deleted region enables a more focused search for other putative tumor suppressor gene at 9p21 which could be relevant to leukemogenesis.
Leukemia 1997 Feb
PMID:The commonly deleted region at 9p21-22 in lymphoblastic leukemias spans at least 400 kb and includes p16 but not p15 or the IFN gene cluster. 900 86

The recent remarkable progress of molecular biology gave us new tools for examination of the etiology and pathology of many diseases. Hence, the introduction of such techniques in our clinical laboratory area is becoming more important and indispensable year by year. In addition to morphological and phenotypical analysis, we are now establishing a molecular diagnosis system to support the clinical diagnosis of hematological malignancies. In the present study, we show our ongoing results focusing on adult T-cell leukemia(ATL). Southern blot analysis for detection of the monoclonal integration of HTLV-I proviral genome, a causative agent of ATL, was performed using digoxigenin-labeled probe. The sensitivity was equivalent to RI-labeled probe and was enough for clinical use. We are also doing Southern blot analysis for immunoglobulin heavy chain gene and T-cell receptor beta chain gene as custom service for the diagnosis of B-lymphoproliferative disorders and non-ATL T-lymphoproliferative disorders. We are reporting such results to the clinical site with our interpretation. Since the band size of the HTLV-I provirus obtained by Southern blot differed in each case and was sometimes smaller than the size of the complete virus, we further analyzed the structure of HTLV-I using long and accurate PCR(LA-PCR) and sequence-target-site PCR(STS-PCR). We found that the integrated HTLV-I provirus is divided into two subtypes, complete virus and defective virus. The incidence of defective virus was high in acute-type ATL compared with that in chronic- or lymphoma-type ATL. Although there are several difficulties in introducing such molecular analyses into the clinical laboratory area, we think that the need is increasing together with the progression of gene therapy and evidence-based medicine.
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PMID:[Southern blot hybridization analysis for lymphoid neoplasms]. 1106 92

The translocation t(11;18)(q21;q21), which is the most frequent chromosomal aberration in extranodal marginal zone B cell lymphomas of MALT-type, was characterised in a series of 34 biopsies, including 18 gastric non-Hodgkin's lymphomas (NHL) of MALT-type, six MALT-type NHL of extragastral origin and 10 extranodal large B cell lymphomas (LBL). Based on fluorescence in situ hybridisation, STS-PCR analysis and screening of genomic PAC libraries, a physical map of contiguous DNA probes on chromosome 11 was constructed containing the anti-apoptotic genes API2 and API1 adjacent to the translocation breakpoint. RACE-PCR experiments revealed MALT1 the chromosome 18-derived fusion partner of API2, which has also been reported recently by other groups. RT-PCR analysis and DNA sequencing demonstrated the expression of an API2-MALT1 fusion transcript in 18/24 gastral and extragastral MALT-type lymphomas. In none of 10 LBLs was a translocation specific RT-PCR product detected. Five variants of the fusion transcript were identified and in all instances the open reading frame of the fused portion of the MALT1 gene was maintained. The molecular analysis of these variants allowed the design of optimised assays for the diagnosis of the API2-MALT1 gene rearrangement.
Leukemia 2000 Nov
PMID:Heterogeneity of the API2-MALT1 gene rearrangement in MALT-type lymphoma. 1106 33

Spontaneous tumors in companion animals (dog and cat) offer a unique opportunity as models for human cancer biology and translational cancer therapeutics. The relatively high incidence of some cancers, similar biologic behavior, large body size, comparable responses to cytotoxic agents, and shorter overall lifespan are the factors that contribute to the advantages of the companion animal model. The tumor types that offer the best comparative interest include lymphoma/leukemia, osteosarcoma, STS, melanoma, and mammary tumors. With the increase in new therapeutic agents (traditional chemotherapy, gene therapy, biologic agents, etc.), the companion animal model can provide useful populations to test new agents where efficacy and toxicity can be examined.
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PMID:Spontaneously occurring tumors of companion animals as models for human cancer. 1110 48

Deletions of regions at 13q14 have been detected by various genetic approaches in human cancers including prostate cancer. Several studies have defined one region of loss of heterozygosity (LOH) at 13q14 that seems to reside in a DNA segment of 7.1 cM between genetic markers D13S263 and D13S153. To define the smallest region of overlap (SRO) for deletion at 13q14, we first applied tissue microdissection and multiplex PCR to detect homozygous deletion and/or hemizygous deletion at 13q14 in 134 prostate cancer specimens from 114 patients. We detected deletions at markers D13S1227, D13S1272, and A005O48 in 13 (10%) of these tumor specimens. Of the 13 tumors with deletions, 12 were either poorly differentiated primary tumors or metastases of prostate cancer. To fine-map the deletion region, we then constructed a high-resolution YAC/BAC/STS/EST physical map based on experimental and database analyses. Several markers encompassing the deletion region were analyzed for homozygous deletion and/or hemizygous deletion in 61 cell lines/xenografts derived from human cancers of the prostate, breast, ovary, endometrium, cervix, and bladder, and a region of deletion was defined by duplex PCR assay between markers A005X38 and WI-7773. We also analyzed LOH at 13q14 in the 61 cell lines/xenografts using the homozygosity mapping of deletion approach and 26 microsatellite markers. We found 24 (39%) of the cell lines/xenografts to show LOH at 13q14 and defined a region of LOH by markers M1 and M5. Combination of homozygous or hemizygous deletion and LOH results defined the SRO for deletion to be an 800-kb DNA interval between A005X38 and M5. There are six known genes located in or close to the SRO for deletion. This region of deletion is at least 2 Mb centromeric to the RB1 tumor-suppressor gene and the leukemia-associated genes 1 and 2, each of which is located at 13q14. These data suggest that the 800-kb DNA segment with deletion contains a gene whose deletion may be important for the development of prostate and other cancers. This study also provides a framework for the fine-mapping, cloning, and identification of a novel tumor-suppressor gene at 13q14.
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PMID:An 800-kb region of deletion at 13q14 in human prostate and other carcinomas. 1159 38

Allelic loss on the chromosome 2 is associated with radiation-induced murine acute myeloid leukemia. However, the gene, which contributes mainly to the leukemogenesis has not yet been identified. Expecting any predisposition to acute myeloid leukemia, we performed a radiation leukemogenensis experiment with Pax6(Sey3H), one of the small eye mutants carrying a congenital hemizygosity of the chromosome 2 middle region. A deletion mapping of Pax6(Sey3H) with 50 STS markers indicated that the deleted segment extended between the 106.00 and 111.47 Mb site from the centromere with a length of 5.47 Mb. In the deleted segment, 6 known and 17 novel genes were located. Pax6(Sey3H) mutants that crossed back into C3H/He did not develop myeloid leukemia spontaneously, but they did when exposed to gamma-rays. The final incidence of myeloid leukemia in mutants (25.8%) was as high as that in normal sibs (21.4%). Survival curves of leukemia-bearing mutants shifted toward the left (p = 0.043 by the Log rank test). F1 hybrids of Pax6(Sey3H) with JF1 were less susceptible to radiation than Pax6(Sey3H) onto C3H/He in regard to survival (p = 0.003 and p < 0.00001 for mutants and normal sibs, respectively, by a test of the difference between two proportions). Congenital deletion of the 5.47 Mb segment at the middle region on chromosome 2 alone did not trigger myeloid stem cells to expand clonally in vivo; however, the deletion shortcut the latency of radiation-induced myeloid leukemia.
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PMID:Spontaneous and radiation-induced leukemogenesis of the mouse small eye mutant, Pax6(Sey3H). 1530 67

Naf1 (Nef-associated factor 1)/TNIP1/ABIN-1 (A20-binding inhibitor of NF-kappaB activation) is a cellular protein that interacts and cooperates with the NFkappaB inhibiting protein A20. It is reported that Naf1 attenuates epidermal growth factor (EGF)/extracellular-signal-regulated kinase2 (ERK2) nuclear signaling. Naf1 also binds to Nef, which plays a key role in acquired immunodeficiency syndrome pathogenesis and HIV-1 virus replication. Naf1 mRNA consists of 18 exons and multiple splice variants have been reported; two isoforms for exon 1, deletion of exon 2 and isoforms alpha and beta for exon 18. Using specimens from 29 acute myeloid leukemia (AML) patients, we detected a high frequency of allelic loss on DNA at STS marker D5S2014 near the Naf1 gene. We therefore performed mutation and expression analyses using leukemia-lymphoma lines and 6 pairs of clinical AML samples. There was no mutation in the Naf1 coding region of any sample. As a result of expression analysis, we identified novel splice variants of the Naf1 gene; deletion of exon 16 (Naf1 alpha2, Naf1 beta2), deletion of exon 16 with an insertion (Naf1 alpha3, Naf1 beta3) and deletion of exons 16 and 17 (Naf1 alpha4). Naf1 alpha3 and beta3 showed premature termination. In peripheral blood mononucleocytes (PBMNCs) from healthy adults, almost no expression of full-length Naf1 (Naf1FL), Naf1 alpha3 and beta3 were observed. In contrast, their expression was clear in AML blasts and in the majority of leukemia-lymphoma lines investigated. Naf1 alpha2 was widely expressed in PBMNCs from healthy adults, AML blasts and cell lines, suggesting it is the main transcript of the Naf1 gene. Luciferase assay revealed that Naf1 alpha2 had equal NF-kappaB inhibitory effect to that of Naf1FL, while Naf1 alpha4 was less effective. In clinical AML patients, the expression of Naf1 alpha3 was much higher at diagnosis than on remission after chemotherapy, suggesting the possible dominant negative effect of Naf1 alpha3.
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PMID:Multiple splicing variants of Naf1/ABIN-1 transcripts and their alterations in hematopoietic tumors. 1701 22


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