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

Mingqiang Ren, Josephine A. Tidwell, Suash Sharma, John Kenneth Cowell

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere38265
JournalPLoS One
Volume7
Issue number6
DOIs
StatePublished - Jun 6 2012

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Myeloproliferative Disorders
B-Lymphoid Precursor Cells
B-lymphocytes
lymphoma
leukemia
Cells
human diseases
B-Cell Leukemia
mice
cell lines
bone marrow
neoplasms
B-Cell Lymphoma
Myeloid Cells
Tumors
Emitter coupled logic circuits
Immunoglobulin M
splenomegaly
lymphocytic leukemia
dimerization

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage. / Ren, Mingqiang; Tidwell, Josephine A.; Sharma, Suash; Cowell, John Kenneth.

In: PLoS One, Vol. 7, No. 6, e38265, 06.06.2012.

Research output: Contribution to journalArticle

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