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

A human Philadelphia-chromosome positive chronic myeloid leukemia-blast crisis (CML-BC) cell line BV173 proliferated in the hematopoietic tissues, infiltrated various organs and caused the death of immunodeficient SCID mice. Leukemia spreading was assessed with diminished number of bone marrow cells and caused splenomegaly. The leukemic colonies grew from single cell suspension of bone marrow, spleen and peripheral blood. Bcr-abl m-RNA was detectable in bone marrow, spleen, peripheral blood, liver, lungs and brain. Dying mice demonstrated severely hypoplastic bone marrow, splenomegaly and massive metastases in the liver and kidneys. The survival time of animals was dependent on the number of inoculated leukemia cells.
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PMID:A model of Ph' positive chronic myeloid leukemia-blast crisis cell line growth in immunodeficient SCID mice. 128 28

B chronic lymphocytic leukemia (CLL) cells were transferred into mice with severe combined immunodeficiency (SCID). Leukemia cells injected into the peritoneal cavity of these animals may survive for at least 10 weeks in vivo. In contrast, leukemia cells do not survive for long periods when injected intravenously. Despite the longevity of CLL cells injected i.p., these cells apparently do not migrate to other lymphoid tissues. Eight to sixteen weeks after receiving CLL cells, SCID mice develop human IgG autoantibodies to human red blood cells and/or high serum levels of human Ig. Soon thereafter, these animals develop lethal human B-cell tumors. In contrast to the original CLL cells, these human B-cell tumors are CD5-negative, have genomic DNA of Epstein-Barr virus (EBV), express antigens associated with latent EBV infection and have distinctive Ig gene rearrangements by Southern. We conclude that bystander B cells may generate tumors in CLL-reconstituted SCID mice that emulate the EBV-associated lymphoproliferations noted in SCID mice reconstituted with normal human PBL.
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PMID:Transfer of human chronic lymphocytic leukemia to mice with severe combined immune deficiency. 138 41

ADA deficiency manifests as a severe combined immunodeficiency with profound T-lymphocytopenia. Affected individuals have variable defects of both T- and B-lymphocyte function and greatly increased morbidity and mortality caused by frequent viral and bacterial infection. In 1990 a clinical protocol for the treatment of this disease using retrovirus mediated transfer of the ADA gene into peripheral lymphocytes was begun and in 1993 an amendment permitting gene transfer to CD34+ stem cells isolated from peripheral blood or from umbilical cord blood was approved. Five patients have been treated on this protocol and have been analyzed for the persistence of cells containing the transferred gene and for immunologic reconstitution.
Leukemia 1995 Oct
PMID:Retrovirus mediated gene transfer as therapy for adenosine deaminase (ADA) deficiency. 747 19

The monoclonal antibody anti-APO-1 induces apoptosis upon triggering the cell surface molecule APO-1 (CD95), a novel member of the tumor necrosis factor/nerve growth factor receptor superfamily. We tested the efficacy of APO-1 mediated apoptosis in a model system of human leukemia in SCID mice. T-ALL cells recovered from SCID mice were sensitive towards anti-APO-1 mediated apoptosis when tested in vitro. In vivo, treatment of leukemia-bearing SCID mice with anti-APO-1 induced programmed cell death in a substantial fraction of T-ALL cells, thus leading to significantly prolonged survival. Anti-APO-1 treatment, however, failed to completely eliminate all leukemic cells. This may be due to resistance towards anti-APO-1 mediated apoptosis in a fraction of T-ALL cells. Thus, identification of cellular programs which determine sensitivity and resistance towards apoptosis may provide new perspectives for rational therapeutic interventions.
Leukemia 1994 Nov
PMID:APO-1 (CD95) mediated apoptosis in human T-ALL engrafted in SCID mice. 752 86

Human mixed lineage leukemia cell line RS4;11 with the t(4;11)(q21;q23) translocation causes disseminated and invariably fatal leukemia in mice with severe combined immunodeficiency. Whereas an immunotoxin constructed from the murine anti-CD19(B43) monoclonal antibody and the plant toxin pokeweed antiviral protein (B43-PAP) has a potent in vitro anti-leukemic effect against clonogenic RS4;11 cells, its activity is further potentiated by the active cyclophosphamide congener mafosfamid. These intriguing observations prompted us to evaluate the in vivo antileukemic efficacy of combined immunochemotherapy employing B43-PAP immunotoxin plus cyclophosphamide against human t(4;11) leukemia cells in an RS4;11 severe combined immunodeficiency (SCID) mouse model system. Intravenous injections of B43-PAP or cyclophosphamide improved survival of SCID mice challenged with RS4;11 leukemia, as reflected by markedly prolonged median survival times. After intravenous inoculation of 5 x 10(7) RS4;11 leukemia cells, the median survival times were 41 days for saline-treated control mice (n = 12), 44 days for control mice treated with unconjugated B43 monoclonal antibody and PAP (n = 12), 56 days for mice treated with the control immunotoxin G17.2 (anti-CD4)-PAP (n = 6), 79 days for B43-PAP-treated test mice (n = 12), and 80 days for cyclophosphamide-treated test mice (n = 16). Notably, combined immunochemotherapy using B43-PAP plus cyclophosphamide was significantly more effective than either B43-PAP or cyclophosphamide alone. The median survival time for a total of 22 SCID mice undergoing combined immunochemotherapy with B43-PAP followed by cyclophosphamide (n = 12) or cyclophosphamide followed B43-PAP (n = 10) was > 150 days. The Kaplan-Meier estimates and standard errors of the probability of event-free survival at 5 months after inoculation of 5 x 10(7) RS4;11 cells were 21 +/- 13% for B43-PAP-treated mice, 7 +/- 6% for cyclophosphamide-treated mice, 90 +/- 10% for mice treated with B43-PAP followed by cyclophosphamide (n = 12), and 90 +/- 10% for mice treated with cyclophosphamide followed by B43-PAP (n = 10). Our results lead us to recommend that initial consideration be given to combined immunochemotherapy protocols using B43-PAP immunotoxin plus cyclophosphamide for treatment of refractory or relapsed t(4;11) leukemias.
Leukemia 1993 Feb
PMID:Effective immunochemotherapy of human t(4;11) leukemia in mice with severe combined immunodeficiency (SCID) using B43 (anti-CD19)-pokeweed antiviral protein immunotoxin plus cyclophosphamide. 767 81

Mice with severe combined immunodeficiency (SCID) were injected with 1 x 10(7) MOLT-3 human T-lineage acute lymphoblastic leukemia cells to provide a model for the evaluation of anti-CD7-pokeweed antiviral protein (PAP) immunotoxin directed against the human CD7 antigen. Of control SCID mice (treated with phosphate-buffered saline, PBS) challenged intravenously with 1 x 10(7) MOLT-3 cells, 5/5 died at 29 to 35 days after inoculation, with a median event-free survival of 33 days. Similarly, 6/6 anti-CD19-PAP treated control SCID mice died of MOLT-3 leukemia at a median of 36 days. In contrast, treatment with anti-CD7-PAP (15 micrograms total dose in 5 micrograms intraperitoneal injections on days 1-3) significantly improved event-free survival of SCID mice challenged with 1 x 10(7) MOLT-3 cells. Of nine SCID mice treated with anti-CD7-PAP, four died at 54-149 days and five remained alive for > 172 days without clinical evidence of leukemia (median event-free survival > 172 days). When long-term survivors among the anti-CD7-PAP treated SCID mice were electively killed at 173 days to assess their leukemia burden, histopathologic examination and polymerase chain reaction provided evidence of disseminated leukemia in some of these mice. Intriguingly, marked differences in morphology, tissue distribution, and histologic pattern of organ invasion existed between leukemic blasts killing 100% of PBS-treated control mice at a median of 33 days and 'therapy-refractory' leukemic blasts detected in anti-CD7-PAP-treated long-term survivors. This novel SCID mouse model of disseminated human T-lineage ALL provides a unique in vivo system to investigate the therapeutic potential of new treatment strategies and to study possible mechanisms of in vivo immunotoxin resistance.
Leukemia 1993 Feb
PMID:In vivo anti-leukemic efficacy of anti-CD7-pokeweed antiviral protein immunotoxin against human T-lineage acute lymphoblastic leukemia/lymphoma in mice with severe combined immunodeficiency. 767 82

Immune deficient SCID mice support the hematopoietic development of surgically implanted human fetal thymus and bone. The usability of the resulting SCID-hu hematolymphoid chimaera as an assay system for human candidate blood stem cells was suggested by the observation that allogeneic CD34+ cells sorted from fetal liver and bone marrow can engraft and differentiate in the transplanted human thymus and bone marrow. The SCID-hu mouse has been further used, in combination with a mouse bone marrow stromal cell line that supports human myeloid and B lymphoid differentiation in vitro, to identify a minor subset of fetal CD34-expressing cells that exhibit multilineage hematopoietic potentialities.
Leukemia 1993 Aug
PMID:Analysis of candidate human blood stem cells in "humanized" immune-deficiency SCID mice. 768 76

Leukemia cell infiltration and the induction of lethal hematopoietic disease in immune-deficient SCID mice transplanted with human T cell acute lymphoblastic T leukemia (T-ALL) cells occurred only when the cells possessed mutant p53 genes and lacked a wild-type allele or when T-ALL cells lacking p53 protein were infected with specific mutant p53 genes. A series of six mutant p53 genes were cloned from relapse T-ALL-derived cell lines and were constructed into defective retroviral expression vectors. Viruses encoding mutant p53 proteins were used to infect relapse T-ALL cells in a study designed to compare their pathogenic potency. The mutant p53 genes possessed a distinct hierarchy in vivo and in vitro: mutants inducing the greatest increase in proliferation of different T-ALL lines in vitro and colony formation in methylcellulose cultures also induced tissue invasiveness of infected T-ALL cells in vivo. Mutant p53 gene transfer to a cell line lacking p53 protein showed that the more potent p53 mutants possessed a distinctive dominant oncogenic activity in vitro and in vivo. The dominant oncogenic activity of these mutant p53 proteins was not dependent on the presence of and on complex formation with wild-type p53 protein. These "hot" p53 mutations thus represent bona fide gain-of-function mutations. Infection of p53-negative T-ALL cells with viruses encoding gain-of-function mutant p53 genes resulted in the acquisition of metastatic potential and tissue invasiveness. Taken together, our results suggest that specific mutant p53 genes play a role in the generation of lymphohematopoietic metastatic potential and tissue invasiveness as assayed in SCID mice, whereas the expression of wild-type p53 is capable of keeping this metastatic potential in check.
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PMID:Gain-of-function mutations of the p53 gene induce lymphohematopoietic metastatic potential and tissue invasiveness. 808 50

Groups of SCID mice were injected with different PBMC sub-populations, and established LCL cells. In about 80% of PBMC-injected animals, tumors developed in association with high levels of human Ig in mouse serum and detectable IL-6 levels. The tumors showed a histopathologic pattern reminiscent of large cell immunoblastic non-Hodgkin's lymphoma; in situ hybridization invariably evidenced EBV sequences in a minority of cells. Genotypic analysis of tumors arising in PBMC-injected mice showed the presence of different oligoclonal B cell populations in different tumor sites. Southern blot analysis disclosed the presence of both linear (replicating) and episomal (latent) EBV DNA forms; sequential analysis of LCL cells serially passaged into animals revealed the progressive selection of clonal cells with only the latent episomal form. Attempts to dissect the events underlying tumor development revealed that the presence of T cells within the injected population was essential for tumor generation; however, the putative T cell-derived factors involved are unclear, and IL-6 seems to play a minor role.
Leukemia 1994 Apr
PMID:Properties of tumors arising in SCID mice injected with PBMC from EBV-positive donors. 815 96

Epstein-Barr Virus (EBV) causes infectious mononucleosis in normal adolescents and malignant B lymphocyte proliferation in immune compromised patients, in marmosets, or upon transfer of infected human B lymphocytes into SCID mice. EBV is also etiologically associated with African Burkitt's lymphoma, Hodgkin's Disease, and nasopharyngeal cancer. EBV transformed, latently infected B lymphocytes contain EBV episomes and eight virus encoded proteins. Six are nuclear proteins (EBNAs) and two are the integral membrane proteins, LMP1 and LMP2. These eight proteins are presumed to mediate latent virus infection or B lymphocyte proliferation and are thus under intense scrutiny. Besides EBNA1, which is required for episome maintenance, LMP1 and LMP2, are the two transformation associated proteins that are most consistently detected in EBV related malignancies, and the LMP2 message is the only message detected in PCR analysis of B lymphocytes from individuals harboring EBV latent infections. LMP2 associates with src family tyrosine kinases, a 70 kda cell phosphoprotein, LMP1 and several other unidentified cell proteins. LMP1 is a key mediator of EBV's effects on inducing B lymphocyte activation and adhesion molecules and is a transforming oncogene in rodent fibroblasts. The association of these two EBV encoded membrane proteins could create a macromolecular complex mediating constitutive B lymphocyte activation through normal cell signal transduction pathways. LMP2 might may control activation of lytic replication or down regulate the activation state of EBV infected cells allowing persistence in the human host.
Leukemia 1994 Apr
PMID:Biochemical and genetic studies of Epstein-Barr virus latent membrane protein 2. 815 3


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