MLL-rearranged leukemias: insights from gene expression profiling.
Gene expression analysis of human leukemias has provided insight into disease classification and mechanisms of oncogenesis. Its success is particularly evident for acute leukemias with rearrangement of the mixed lineage leukemia (MLL) gene on chromosome 11q23. Unlike most other recurrent translocations, MLL rearrangements are found in leukemias classified as acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL). In addition, MLL-rearranged leukemias often express both myeloid- and lymphoid-associated genes. These unusual characteristics have generated much interest in the cell of origin and the mechanism of transformation by MLL rearrangements. Here we review insights gained from characterization of MLL-rearranged human leukemias by genome-wide expression profiling and compare these to data from model systems.
Armstrong
Scott A
SA
Department of Pediatric Oncology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Golub
Todd R
TR
Korsmeyer
Stanley J
SJ
D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051788:Myeloid-Lymphoid Leukemia Protein; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014157:Transcription Factors; D014178:Translocation, Genetic; D051941:fms-Like Tyrosine Kinase 3
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3