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The Oncoprotein MLL–ENL disturbs hematopoietic lineage determination and transforms a biphenotypic lymphoid/myeloid cell
- Source :
- Oncogene. 22:1629-1637
- Publication Year :
- 2003
- Publisher :
- Springer Science and Business Media LLC, 2003.
-
Abstract
- Mixed-lineage leukemia (MLL) fusion proteins are associated with a unique class of leukemia that is characterized by the simultaneous expression of lymphoid-specific as well as myeloid-specific genes. Here we report the first experimental model of MLL. Murine bone marrow cells were retrovirally transduced to express the MLL-eleven nineteen leukemia (MLL-ENL) fusion protein. When cultivated in flt-3 ligand, stem cell factor and interleukin-7 (IL-7) in a stroma-free culture system MLL-ENL-transduced as well as control cells showed a wave of B-lymphopoiesis. Whereas the controls exhausted their proliferative capacity in a CD19+/B220+ state, a continuously proliferating CD19-/B220+ cell population emerged in the MLL-ENL-transduced cultures. Despite the lymphoid surface marker, these cells were of monocytoid morphology. The immortalized cells contained unrearranged retrovirus, expressed MLL-ENL mRNA and were able to grow in syngenic recipients. From the diseased animals an MLL-ENL positive, B220+/CD19- cell type could be reisolated and cultivated in vitro. In analogy to human MLL, MLL-ENL-transformed cells not only coexpressed lymphocyte-specific (rag1, rag2, pax5, Tdt) and monocyte-specific genes (lysozyme, c-fms), but also showed rearrangements of the genomic immunoglobulin locus. This model shows that MLL-ENL influences events of early lineage determination and it will enable the investigation of the underlying molecular processes.
- Subjects :
- Cancer Research
Myeloid
Oncogene Proteins, Fusion
Bone Marrow Cells
Stem cell factor
CD19
Mice
hemic and lymphatic diseases
Genetics
medicine
Animals
Cell Lineage
neoplasms
Molecular Biology
biology
Reverse Transcriptase Polymerase Chain Reaction
Cell Differentiation
hemic and immune systems
3T3 Cells
medicine.disease
Fusion protein
Virology
Molecular biology
Blotting, Southern
Leukemia
Haematopoiesis
medicine.anatomical_structure
Cell culture
biology.protein
Bone marrow
Myeloid-Lymphoid Leukemia Protein
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....ff38da31d2f729572b47fd4723e37250