Project description:We report the genome wide distribution of H3K79 dimethylation in mouse MLL-AF6 positive leukemias to assess whether this epigenetic mark drives MLL-target gene expression. Examination of H3K79 dimethylation in bone marrow cells from sacrificed terminally ill MLL-AF6 positive leukemic mice. The retroviral MSCV-IRES-neo-MLL-AF6 construct was transduced into mouse bone marrow lineage negative Kit +, Sca + (LSK) cells and these cells were injected after G418 selection into irradiated syngenic mice to establish MLL-AF6 positive leukemias.
Project description:[original title] Gene expression analysis of leukemic samples derived from AF4-MLL- or AF4-MLL/MLL-AF4-transduced and transplanted hematopoietic stem/precursor cells in C57BL6 mice. We used microarrays to analyze the global gene expression in leukemic cells with three distinct immunophenotypes. We compared leukemic cells isolated from the bone marrow of diseased mice and compared these profiles with normal bone marrow.
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. Keywords: Cell type comparison
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. Keywords: Cell type comparison
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. Keywords: Cell type comparison
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Immunophenotypic and gene expression analysis of the ALL cells demonstrated bone marrow replacement with B-precursor cells which express a gene expression profile that has significant overlap with profiles in human MLL-rearranged ALL. To examine early, pre-leukemic changes in lymphoid cells due to Mll-AF4 expression, we infected 5-FU bone marrow cells from Mll-AF4stop knocking mice with activating (Cre-GFP) or control (MIF-GFP) retrovirus ex vivo and measured expression changes after culture under lymphoid growth conditions. Experiment Overall Design: Mll-AF4stop knock-in mice were treated with 5-FU and 5 days later their bone marrow infected ex vivo with either Cre-GFP to activate the Mll-AF4 fusion construct or with a control MIG-Cre retrovirus. GFP+ cells were sorted 2 days post-infection and cultured for 14 days under lymphoid growth conditions before total RNA was isolated for hybridization to Affymetrix expression microarrays.
Project description:We report the genome wide distribution of H3K79 dimethylation in the human MLL-AF6 rearranged cell line ML2 as well as the human MOLM13 and HL60 cell lines Examination of H3K79 dimethylation in the MLL-AF6 fusion positive human leukemia cell line ML2 and control cell lines MOLM-13 and HL60. The MLL-AF6 positive ML2 cell line (obtained from DSMZ) and the cell lines HL60 and MOLM 13 were grown under standard conditions and 1 million cells were fixed/crosslinked and used for ChIP-seq with H3K79 dimethylation specific antibody Ab3594 (Abcam)
Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Immunophenotypic and gene expression analysis of the ALL cells demonstrated bone marrow replacement with B-precursor cells which express a gene expression profile that has significant overlap with profiles in human MLL-rearranged ALL. To examine early, pre-leukemic changes in lymphoid cells due to Mll-AF4 expression, we infected 5-FU bone marrow cells from Mll-AF4stop knocking mice with activating (Cre-GFP) or control (MIF-GFP) retrovirus ex vivo and measured expression changes after culture under lymphoid growth conditions. Keywords: Cell type comparison
Project description:We report the genome wide distribution of H3K79 dimethylation in mouse MLL-AF6 positive leukemias to assess whether this epigenetic mark drives MLL-target gene expression.