Homeobox genes in hematopoiesis and leukemogenesis.
Homeobox genes have a strikingly conserved 61-amino acid sequence, encoding DNA-binding domain. Some homeobox genes, located in four clusters are designated HOX A through D, while others are known as divergent homeobox genes. Many researchers have demonstrated that hematopoietic cells express many homeobox genes. Induced over- and under-expression of these genes has been used to demonstrate their affect on some aspects of hematopoiesis and leukemogenesis. Recently, knock-out mice of homeobox genes by targeted disruption have also been used to examine their hematological effect. There are examples of the aberrant expression of a homeobox gene causing leukemias in humans. In pre-B acute lymphoblastic leukemia (ALL) with t(1;19) translocation, a fusion protein is created between E2A and a homeobox gene PBX. In T-cell ALL with t(10;14) translocation, the HOX 11 gene is deregulated. In acute myeloid leukemia (AML) with t(7;11) translocation, the HOX A9 gene is rearranged. In this review article, many functions of homeobox genes both at the early stem cell level as well as at the later stages of hematopoietic differentiation, and the leukemogenic effect of altered homeobox genes are discussed.
First Department of Internal Medicine, Tokyo Medical College, Japan. takashis@cb3.so-net.or.jp
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D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology; D005314:Embryonic and Fetal Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D005801:Genes, Homeobox; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D007942:Leukemia, Experimental / Q000235:genetics / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D013045:Species Specificity; D013234:Stem Cells / Q000378:metabolism; D009626:Terminology as Topic; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; C089847:E2A-Pbx1 fusion protein