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

Adult T cell leukemia (ATL) cells show the decreased expression of T cell receptor (TCR)/CD3 complex on their surfaces in vivo. It is well known that excess amounts of antigen modulate TCR/CD3 complex on antigen-specific T lymphocytes. We hypothesized that antigen receptor of ATL cells was down-regulated with some antigenic stimulation in vivo, which might play an important role in leukemogenesis. In order to test this possibility, we studied whether the fresh ATL cells from three cases would respond to autologous and allogeneic lymphoid cell lines. In two of three cases, ATL cells could proliferate in the presence of autologous cell lines. In one case, this proliferation could be completely inhibited by anti-CD3 and anti-human leukocyte antigen (HLA)-DQ monoclonal antibodies, indicating that ATL cells recognized self HLA-DQ. In another case, the proliferation was suppressed by anti-CD3 and HLA-DR antibodies. These findings showed that ATL cells of some cases were derived from autoreactive T lymphocytes and such stimulation via TCR/CD3 complex plays an important role in the leukemogenesis of ATL in vivo.
Leukemia 1995 Aug
PMID:ATL cells recognize self class II HLA antigens: implication to leukemogenesis. 764 22

Homeobox genes encode for sequence-specific DNA-binding proteins which have been implicated in the control of gene expression during development and in certain adult tissues. Two recently characterized human homeobox-containing genes, HB9 and HB24, are known to be expressed in hematopoietic progenitors and to be involved in the regulation of growth and differentiation of progenitor cells to mature hematopoietic cell types. In this study, elevated levels of HB24 and HB9 mRNA expression were detected in bone marrow and peripheral blood mononuclear cells (PBMC) isolated from patients with acute myelogenous or acute lymphocytic leukemia. While the levels of both mRNAs were elevated in all the patients with acute leukemias, the levels of HB9 mRNA were more variable than those of HB24. Immunohistochemical analysis utilizing an HB24 polyclonal antiserum demonstrated elevated levels of HB24 protein in cytopreparations of acute leukemic cells. Nuclear run-on experiments showed that the increases of HB9 and HB24 mRNA transcripts in patients' cells were, at least in part, secondary to increased transcription. The expression of HB9 and HB24 correlated with the clinical status of the patient. No significant level of expression of either HB9 or HB24 was detected in PBMC isolated from patients in remission. In contrast to the findings with cells isolated from patients with acute leukemias, no significant increase in either HB9 or HB24 transcript levels were found in cells from patients with chronic lymphocytic or chronic myelogenous leukemia when compared to normal controls. These findings demonstrate that high levels of HB9 and HB24 expression are common features of acute leukemia and suggest the possibility that the dysregulated expression of these two genes may contribute to leukemogenesis. However, since these two genes are markers of immature hematopoietic cells they may not have an etiologic role in leukemogenesis.
Leukemia 1993 Mar
PMID:High expression of two diverged homeobox genes, HB24 and HB9, in acute leukemias: molecular markers of hematopoietic cell immaturity. 768 Apr 2

Bone marrow transplantation experiments were conducted in mice in order to develop an experimental bone marrow transplantation therapy model, with which to investigate possible means to cure retrovirus-infected hosts with bone marrow or stem cells from virus-resistant donors. In one experiment, lethally irradiated Friend leukemia virus (FLV)-sensitive C3H/He (C3H; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s Rfv-3s) mice were transplanted with (i) bone marrow cells from FLV-resistant BALB/c-Fv-4Wr (C4W; Fv-2s, Fv-4r, Rfv-1s, Rfv-2s, Rfv-3s) mice (C4W --> C3H) or (ii) a mixture of bone marrow cells from C4W and C3H mice (C4W + C3H --> C3H). They were then inoculated with FLV 3-4 months later and leukemia development was examined. The results indicated that C4W --> C3H chimeras were completely resistant to FLV-induced leukemogenesis and that C4W + C3H --> C3H mixed chimeras that contained as low as 30% C4W-derived cells, or as high as 70% C3H-derived cells, did not develop leukemias. In another experiment, bone marrow cells from C57BL/6 (B6; Fv-2r, Fv-4s, Rfv-1r, Rfv-2r, Rfv-3r) or C4W donors were grated to FLV-sensitive DBA/2 mice (DBA; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s, Rfv-3s) that had been infected with FLV 6 days earlier (DBA-FLV). The results indicated that most, if not all, FLV-infected DBA mice which received bone marrow transplantation from B6 donors developed B6-derived leukemias, although the survival time of these mice was dramatically prolonged as compared to that of untreated DBA-FLV mice. In contrast, bone marrow transplantation from Fv-4r-bearing C4W donors successfully rescued FLV-infected DBA mice from leukemic deaths. Thus, the bone marrow transplantation therapy against retroviral infection of hemopoietic cells was shown to be feasible, provided that donor cells carry a resistant allele that functions via receptor blockade as in the case of Fv-4r, but less effective when the roles of the resistant alleles partially interfered with the virus replication, leukemic transformation and/or cycling of target cells as suggested for Fv-2r gene action, or to resist virus infection by immunological means as are known for Rfv-1r, Rfv-2r and Rfv-3r genes which are also carried by B6-strain mice. Implication of these findings on the somatic gene therapy against retrovirus infection diseases in man are discussed.
Leukemia 1994 Dec
PMID:Bone marrow transplantation from Fv-4-resistant donors rescues Friend leukemia virus-infected mice from leukemia: a model of bone marrow transplantation therapy against retroviral infection. 780 8

By genetically manipulating hematopoietic cells of the myeloid lineage, including both normal cells and differentiation inducible leukemic cell lines, evidence was obtained to indicate that myeloid differentiation primary response (MyD) genes and proto-oncogenes, which are known to control cell growth, function as positive and negative regulators of terminal hematopoietic cell differentiation, which is associated with inhibition of cell growth, and, ultimately programmed cell death (apoptosis). Interferon regulatory factor-1 (IRF-1), an MyD gene induced by Interleukin 6 (IL-6) or Leukemia Inhibitory factor (LIF), plays a role in growth inhibition associated with terminal differentiation. Leucine zipper transcription factors of the fos/jun family, also identified as MyD genes, function as positive regulators of hematopoietic cell differentiation, increasing the propensity of myeloblastic leukemia cells to be induced for differentiation in vitro, and reducing the aggressiveness of their leukemic phenotype in vivo. The zinc finger transcription factor EGR-1, an MyD gene specifically induced upon macrophage differentiation, was shown to be essential for and to restrict differentiation along the macrophage lineage. Finally, evidence has been accumulating to indicate that the novel MyD genes--MyD116, MyD118 and gadd45 (a member in the MyD118 gene family)--play a role in growth arrest and apoptosis of hematopoietic cells, as well as other cell types. The proto-oncogenes c-myc and c-myb, known to regulate cellular growth, were shown to function as negative regulators of terminal differentiation. Both c-myc and c-myb are normally expressed in proliferating myeloblasts and suppressed following induction of differentiation. Deregulated and continuous expression of c-myc was shown to block terminal myeloid differentiation at an intermediate stage in the progression from immature blasts to mature macrophages, whereas deregulated and continuous expression of c-myb blocked the terminal differentiation program at the immature myeloblast stage. By manipulating myc function in conditional (differentiation inducible) mutant myeloblastic leukemia cell lines, expressing a chimeric mycer transgene, it was shown that there is a window during myeloid differentiation, after the addition of the differentiation inducer, when the terminal differentiation program switches from being dependent on c-myc suppression to becoming c-myc suppression independent, and where activation of c-myc has no apparent effect on mature macrophages. These myeloblastic leukemia cell lines provide a powerful tool to increase our understanding of the role of c-myc in normal hematopoiesis and in leukemogenesis, while also providing a strategy to clone myc target genes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differentiation primary response genes and proto-oncogenes as positive and negative regulators of terminal hematopoietic cell differentiation. 795 Oct 3

Two Arab children from the Gaza strip presented with fever, weakness, hepatosplenomegaly, lymphadenopathy and leukocytosis. The peripheral and bone marrow blasts had an immunophenotype compatable with T-cell acute lymphoblastic leukemia, and exhibited unusual markers (CD2+, CD3+, CD4-, CD8-). Cytogenetic studies revealed t(8;14)(q24;q11), possibly involving the alpha/delta locus of the T-cell receptor gene on chromosome 14 rather than the immunoglobulin heavy-chain locus usually involved in the t(8;14)(q24;q32), which is typical for Burkitt's leukemia/lymphoma. One of the children had a brother who died of T-cell acute lymphoblastic leukemia a few years later, however, his blasts showed deletion of chromosome 12. The possible role for environmental factors associated with low socioeconomic status, as well as of genetic factors in leukemogenesis are discussed.
Leukemia 1994 Nov
PMID:Lymphomatous T-cell leukemia in two Arab children. Is there a role for an environmental effect. 796 44

Patients with Fanconi anemia (FA) have an extraordinary predisposition to acute myelogenous leukemia (AML). The genetic mechanisms underlying the neoplastic transformation of FA hematopoietic cells are unknown. In this study, we have investigated the molecular features of hematopoiesis in the course of FA at different stages of the disease, including aplastic anemia, myelodysplastic syndrome (MDS), and AML. The analysis focused on defining the clonality status of FA hematopoiesis as well as the putative involvement of N-ras, a dominantly acting oncogene, and p53, a tumor suppressor gene, which are known to play a role in human hematopoietic tumors. Clonality of hematopoiesis was assessed by testing X-chromosome inactivation at the DXS255 locus, which displays different methylation patterns according to the activation status of the corresponding X homolog. Five out of seven FA cases analysed for clonality displayed monoclonal hematopoiesis, including one case at the aplastic anemia stage, three cases with MDS and one with AML. Mutations of the N-ras and p53 genes were studied by a combination of single strand conformation polymorphism (SSCP) analysis and direct sequencing of the PCR product in the bone marrow and/or peripheral blood of 18 FA patients (seven with aplastic anemia, seven with MDS, four with AML). Only normal N-ras and p53 sequences were detected in all cases analyzed. These results suggest that monoclonal hematopoiesis is a frequent finding in the course of FA and may precede the onset of neoplasia in some cases. The genetic mechanisms underlying FA-associated leukemogenesis appear to be independent of N-ras and p53 mutations, which are relatively frequent events in myeloid tumors associated with other hematologic disorders.
Leukemia 1994 Aug
PMID:Clonality studies and N-ras and p53 mutation analysis of hematopoietic cells in Fanconi anemia. 805 73

Uncontrolled proliferation of acute myeloid leukemia (AML) cells is an important step during leukemogenesis. However, little is known about the mechanisms leading to growth autonomy. Studies using immortalized murine hematopoietic cell lines have suggested that autocrine production of growth factors, or the constitutive activation of molecules in growth factor signalling pathways, are involved. We have established six spontaneous factor-independent cell lines from the human growth factor-dependent TF-1 cell line. The factor-independent cells showed no detectable growth factor activity. Immunoblotting analyses of tyrosine phosphorylation, Raf-1 and extracellular signal-regulated kinase 2 (ERK-2) showed a similar pattern in all the cell lines including TF-1 cells. Furthermore, somatic-cell hybrids between TF-1 and the factor-independent cells grew in absence of growth factor. Taken together this data demonstrates that the factor independence in this system is dominant and suggests that the molecular event is located either downstream of the Raf-1 and MAP kinases pathway or on an alternative pathway. Finally, the karyotype analysis of one factor-independent cell line TF-1i1 and TF-1H- (G418 resistant, HAT sensitive TF-1 cells) and their hybrids demonstrated an unstable derivative chromosome [der(19) t(19;?) (q13.1;?)] which seemed to correlate with the factor-independence capacity. This model may help in our understanding of autonomous proliferation by human myeloid leukemias.
Leukemia 1994 Aug
PMID:Characterization of spontaneous factor-independent cell lines derived from the human leukemic cell line TF-1: a dominant event. 805 74

The differentiative capacity of a unique haematopoietic cell type has been investigated. These cells have been found to be a common target in vitro to infection and immortalization by radiation leukemia viruses (RadLVs). Many continuous lines of these cells have been generated. Since RadLV retroviruses are known to be strictly T-cell-tropic in vivo, we have questioned whether these cells are precursors of T cells. To this end, the RadLV-induced C1-V13D cell line has been inoculated into thymus of sublethally irradiated syngeneic CBA/H mice and tested for capacity to proliferate and differentiate, i.e. express T-cell markers. When inoculated in high number, C1-V13D cells can induce a thymic tumour within 14 to 21 days. Expression of T-cell markers on these cells was determined by fluorescence-activated cell sorting (FACS) analysis, after gating out C1-V13D cells on the basis of their high 90 degree scatter and their high forward scatter. They can also be distinguished by their unique expression of RadLVgp70 envelope (env) protein, B220, CD44, and aberrant expression of a class I epitope. Explanted primary thymomas from many animals showed no evidence of T-cell marker expression on C1-V13D cells upon reisolation. However, when C1-V13D was further passaged intrathymically, there was clear expression of Thy-1, CD4, CD8, and TCR-alpha beta on C1-V13D cells reisolated from these tumours. Two-colour FACS analysis and fluorescent antibody staining have confirmed the acquisition of T-cell surface markers by C1-V13D cells growing in this environment. Northern analysis confirmed endogenous expression of T-cell receptor beta chain genes in C1-V13D cells isolated after the third passage. All data indicate that RadLV preferentially infects a unique haematopoietic precursor cell in spleen which can differentiate along the T lineage once located within the thymic environment. The cell lines described here represent valuable models for studying T-cell differentiation from lymphoid stem cells, and for dissecting the early events in leukemogenesis.
Leukemia 1993 Aug
PMID:T-cell differentiative capacity of haematopoietic stem cells immortalized in vitro with radiation leukemia virus. 810 19

Bone marrow monosomy 7 (Mo 7) is associated with childhood preleukemic myeloproliferative and myelodysplastic syndromes (MPS and MDS). We used a series of polymorphic markers to investigate the parental origins of chromosomes lost from the bone marrows of 12 children with MPS/MDS and Mo 7. Eight Mo 7 bone marrows lost a maternal chromosome 7 and four cases lost the paternal homologue. Our data and the results of previous laboratory and clinical observations in the familial and sporadic forms of childhood Mo 7 suggest that chromosome 7 deletions contribute to leukemogenesis by gene dosage.
Leukemia 1994 Mar
PMID:Parental origins of chromosome 7 loss in childhood monosomy 7 syndrome. 812 52

Members of the NF-kappa B/Rel family of transcription factors are involved in the transcriptional regulation of numerous polypeptides important to the immune response and cellular growth. Several genes regulated in part by NF-kappa B/Rel such as interleukin 2, IL-2 receptor alpha, and GM-CSF are trans-activated via an indirect association with the HTLV-I Tax protein in virus-infected and transformed T cells. In this study, we have investigated the interactions between Tax and NF-kappa B/Rel in an attempt to elucidate the mechanism of Tax mediated trans-activation and its role in leukemogenesis. Transfection studies were performed in Jurkat T cells using expression vectors for individual NF-kappa B subunits and the Tax protein as well as an NF-kappa B regulated reporter plasmid. NF-kappa B proteins differentially trans-activated the HIV-1 enhancer-CAT reporter; co-expression of Tax abrogated the inhibitory effect of I kappa B alpha and a trans-dominant negative mutant of p65 (p65 delta), indicating that Tax was a trans-dominant activator of NF-kappa B-regulated genes. Co-immunoprecipitation studies with extracts from transfected cells and NF-kappa B and Tax subunit specific antibodies revealed that Tax did not co-immunoprecipitate with p50/p105, c-Rel, or I kappa B; however, antibody specific to p65 was able to co-immunoprecipitate a 40kDa protein from Tax-transfected cells. Previous studies have demonstrated a physical interaction between Tax protein and p100, indicating that Tax may preferentially associate with specific NF-kappa B proteins.
Leukemia 1994 Apr
PMID:Interactions between HTLV-I Tax and NF-kappa B/Rel proteins in T cells. 815 9


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