BCR-FGFR1 simultaneously induces B-cell leukemia/lymphoma and myeloid proliferative disorder.

<p>Representative flow cytometric analysis of bone marrow (A), spleen (B) and peripheral blood (C) cells from primary transplanted mouse #5 with BCR-FGFR1-induced disease shows that the majority of B-cells are arrested at pro-B stage with a CD19⁺IgM⁻ immunophenotype in both GFP positive and negative cells. The presence of GFP⁺Mac-1⁺Gr-1⁺ populations, as well as high levels of GFP⁻Mac-1⁺Gr-1⁺ cells, was also seen. Very few T-lineage (CD4⁺ and/or CD8⁺) cells were present in the leukemic spleen. GFP expression was lost in the peripheral blood from the majority of primary recipients, where the BCR-FGFR1 fusion transcript can be detected by RT-PCR (C, below). D) Most of the primary transplanted mice showed enlarged lymph nodes and/or tumors in their abdomens. Representative flow cytometric analysis of the tumor cells shows the predominantly pro-B lymphoma immunophenotype, CD19⁺IgM⁻. E) Schematic diagram showing the progression of B-cell development from hematopoietic stem cells (HSC) and common lymphoid progenitors (CLP) into mature B cells and plasma cells. The immunophenotype of the B-lineage cells carrying the BCR-FGFR1 fusion kinase suggests an arrest at the pro-B stage of development as indicated.