Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage.
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.
Georgia Health Sciences University Cancer Center, Georgia Health Sciences University School of Medicine, Augusta, Georgia, United States of America.
Mingqiang
M
Ren
Josephine A
JA
Tidwell
Suash
S
Sharma
John K
JK
Cowell
D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000276:immunology / Q000502:physiology*; D055028:Comparative Genomic Hybridization; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D006652:Histological Techniques; D007075:Immunoglobulin M / Q000276:immunology; D016130:Immunophenotyping; D007621:Karyotyping; D015448:Leukemia, B-Cell / Q000209:etiology / Q000503:physiopathology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D051917:Leukosialin / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009196:Myeloproliferative Disorders / Q000209:etiology / Q000503:physiopathology*; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018941:Antigens, CD19; D017931:DNA Primers; D007075:Immunoglobulin M; D051917:Leukosialin; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017493:Leukocyte Common Antigens