Expression data from ZMYM2-FGFR1-induced T-cell lymphomas in a mouse model

The ZMYM2-FGFR1 (formerly known as ZNF198-FGFR1) fusion kinase induces stem cell leukemia-lymphoma syndrome (SCLL), a hematological malignancy characterized by rapid transformation to acute myeloid leukemia and T-lymphoblastic lymphoma. We previously developed a mouse model of ZMYM2-FGFR1 (Ren et al. 2009, Blood). To further investigate mechanisms of oncogenesis and progression, we undertook a global gene expression analysis of leukemic T-cells from the animal model compared with Thy1+DP+ (CD4+CD8+) cells isolated from normal Balb/c thymuses, as well as lukemic stem cells (LSK, GFP+Lin-Sca-1+c-kit+ cells) sorted from the leukemic mice versus hematopoietic stem cells (HSC, Lin-Sca-1+c-kit+ cells) sorted from normal BALB/c bone marrow cells. We found high expressions of Notch1 and its downstream target genes in T-cell lymphomas that arise in a murine model of ZMYM2-FGFR1 SCLL. Our functional studies demonstrate the importance of Notch signaling in the etiology of SCLL and suggest that targeting this pathway could provide a novel strategy for molecular therapies to treat SCLL patients. RNA was isolated from HSC (Lin-Sca-1+c-kit+) sorted from normal BALB/c bone marrow cells and lukemic stem cells (LSK, GFP+ Lin-Sca-1+c-kit+ cells) sorted from the leukemic mice bone marrow or spleen cells. To minimize biological variability, each HSC sorting experiment used BM cells from 5 normal female Balb/c. LSC were obtained from BM or spleen cells from 2-3 leukemic mice. Gene expression profiles of T-lymphoma and Thy1+DP+ (CD4+CD8+) cells were obtained from three independently sorted Thy1+DP+ cell samples (each sample was derived from thymuses from 3 normal Balb/c mice). The T-lymphoma samples were derived from third serial transplanted disease mice, where >90% of cells were GFP+Thy1+DP+. To investigate whether the sorting process influenced gene expression, one T-lymphoma sample was sorted for GFP+Thy1+DP+ cells. RNA was amplified using a GeneChip Two-Cycle Target Labeling and Control Reagents kit (Affymetrix), and cRNA was hybridized to the Affymetrix Mouse430 2.0 arrays.