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Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage.

ABSTRACT: Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that both showed bi-lineage involvement of myeloid and B-cells, splenomegaly, leukocytosis and bone marrow hypercellularity. A CD19(+) IgM(-) CD43(+) immunophenotype was seen both in primary tumors and two cell lines derived from these tumors. In all primary tumors, subpopulations of these CD19(+) IgM(-) CD43(+) were also either B220(+) or B220(-), suggesting a block in differentiation at the pro-B cell stage. The B220(-) phenotype was retained in one of the cell lines while the other was B220(+). When the two cell lines were transplanted into syngeneic mice, all animals developed the same B-lymphoblastic leukemia within 2-weeks. Thus, the murine model described here closely mimics the human disease with bilineage myeloid and B-cell leukemia/lymphoma which provides a representative model to investigate therapeutic intervention and a better understanding of the etiology of the disease.

SUBMITTER: Ren M

PROVIDER: S-EPMC3368885 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage.

Ren Mingqiang M Tidwell Josephine A JA Sharma Suash S Cowell John K JK

PloS one 20120606 6

Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that ...[more]

PMID: 22701616

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Project description:Dengue (DEN) is the most prevalent arbovirus among humans, and four billion people live at risk of infection. The clinical manifestations of DEN are variable, and the disease may present subclinically or asymptomatically. A quarter of patients develop classical dengue (CD) or severe dengue (SD), which is potentially lethal and involves vascular permeability changes, severe hemorrhage and organ damage. The involvement of the liver is a fairly common feature in DEN, and alterations range from asymptomatic elevation of transaminases to acute liver failure. Since its introduction in Brazil in 1990, two strains of Dengue virus (DENV) serotype 2 (DENV-2) have been detected: Lineage I, which is responsible for an outbreak in 1991, and Lineage II, which caused an epidemic greater than the previous one and had a different epidemiological profile. To date, studies on different strains of the same serotype/genotype and their association with disease severity are scarce. In addition, one of the greatest challenges regarding the study of DEN pathogenesis and the development of drug and vaccine therapies is the absence of an animal model that reproduces the disease as it occurs in humans. The main goals of this study were to assess BALB/c mouse susceptibility experimentally infected by two distinct DENV-2 strains and characterize possible differences in the clinical signs and alterations induced in the liver resulting from those infections. Mice infected by the two DENV-2 lineages gained less weight than uninfected mice; however, their livers were slightly heavier. Increased AST and AST levels were observed in infected mice, and the number of platelets increased in the first 72 h of infection and subsequently decreased. Mice infected with both lineages presented leukocytosis but at different times of infection. The histopathological changes induced by both lineages were similar and comparable to the changes observed in DEN fatal cases. The viral genome was detected in two liver samples. The results demonstrate the susceptibility of BALB/c mice to both DENV-2 lineages and suggest that the changes induced by those strains are similar, although for some parameters, they are manifested at different times of infection.

Dataset Information

Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage.

Publications

Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage.

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