The role of the MLL gene in infant leukemia.
The MLL gene is a major player in leukemia, particularly in infant leukemia and in secondary, therapy-related acute leukemia. The normal MLL gene plays a key role in developmental regulation of gene expression (including HOX genes), and in leukemia this function is subverted by breakage, recombination, and chimeric fusion with one of 40 or more alternative partner genes. In infant leukemias, the chromosome translocations involving MLL arise during fetal hematopoiesis, possibly in a primitive lymphomyeloid stem cell. In general, these leukemias have a very poor prognosis. The malignancy of these leukemias is all the more dramatic considering their very short preclinical natural history or latency. These data raise fundamental issues of how such divergent MLL chimeric genes transform cells, why they so rapidly evolve to a malignant status, and what alternative or novel therapeutic strategies might be considered. We review here progress in tackling these questions.
Eguchi
Mariko
M
LRF Centre for Cell and Molecular Biology of Leukaemia, Institute of Cancer Research, London, UK.
Eguchi-Ishimae
Minenori
M
Greaves
Mel
M
D000208:Acute Disease; D017668:Age of Onset; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D018450:Disease Progression; D015195:Drug Design; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000196:embryology / Q000453:epidemiology / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D051788:Myeloid-Lymphoid Leukemia Protein; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics; D011519:Proto-Oncogenes; D013329:Structure-Activity Relationship; D014157:Transcription Factors; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse