Insertional mutagenesis and transformation of hematopoietic stem cells.
The mechanisms that are involved in the control of the normal differentiation of hematopoietic progenitor cells are largely unknown. Moreover, little is known concerning the types of genes that can alter the ability of hematopoietic progenitors to differentiate and cause transformation. One approach to the latter has been to use retroviral induced IL-3-dependent myeloid leukemia cell lines to identify transforming genes by their activation through insertional mutagenesis. This approach has implicated alterations in c-myb in transformation and has identified a novel transcriptional factor of the zinc finger family that is frequently activated in murine myeloid leukemias and in some cases of human AML. Using this approach it should be possible to identify additional myeloid transforming genes. The identification and characterization of the genes will provide important information and approaches to the study of the regulation of differentiation in normal hematopoiesis.
Ihle
J N
JN
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105.
Morishita
K
K
Matsugi
T
T
Bartholomew
C
C
D000208:Acute Disease; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002472:Cell Transformation, Viral; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000502:physiology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes; D011995:Recombination, Genetic; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D007377:Interleukin-3; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C499305:Mecom protein, mouse; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D014157:Transcription Factors