Homeobox Gene Expression Plus Autocrine Growth Factor Production Elicits Myeloid Leukemia

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1990 Nov 1

PMID 1978323

Citations 39

Authors

A Perkins

K Kongsuwan

J Visvader

J M Adams

S Cory

Affiliations

Soon will be listed here.

Abstract

In the murine myelomonocytic leukemia WEHI-3B, proviral insertions have induced expression of the Hox-2.4 homeobox gene and the gene for the myeloid growth factor interleukin 3 (IL-3). To assess their potential oncogenic role, normal bone marrow cells were infected with retroviruses bearing the genes for IL-3 or IL-3 plus Hox-2.4. Unlike the IL-3 virus, the IL-3/Hox-2.4 virus was highly leukemogenic. Infected cells expressing both genes exhibited retarded differentiation in vitro, generated myelomonocytic cell lines, and provoked a rapid, transplantable myeloid leukemia in vivo. The oncogenic action of Hox-2.4 appears to derive from its ability to impede the IL-3-driven terminal differentiation of myeloid cells. The results suggest that homeobox genes can regulate key differentiation processes such as self-renewal capacity and that their inappropriate expression can be oncogenic.

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References

Warner N, Moore M, Metcalf D . A transplantable myelomonocytic leukemia in BALB-c mice: cytology, karyotype, and muramidase content. J Natl Cancer Inst. 1969; 43(4):963-82. View

Kamps M, Murre C, Sun X, Baltimore D . A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL. Cell. 1990; 60(4):547-55. DOI: 10.1016/0092-8674(90)90658-2. View

Hodgson G, Bradley T . Properties of haematopoietic stem cells surviving 5-fluorouracil treatment: evidence for a pre-CFU-S cell?. Nature. 1979; 281(5730):381-2. DOI: 10.1038/281381a0. View

Dexter T, Garland J, Scott D, Scolnick E, Metcalf D . Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980; 152(4):1036-47. PMC: 2185980. DOI: 10.1084/jem.152.4.1036. View

Mann R, Mulligan R, Baltimore D . Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983; 33(1):153-9. DOI: 10.1016/0092-8674(83)90344-6. View

Rabin M, Hart C, A Ferguson-Smith , McGinnis W, Levine M, Ruddle F . Two homoeo box loci mapped in evolutionarily related mouse and human chromosomes. Nature. 1985; 314(6007):175-8. DOI: 10.1038/314175a0. View

Ymer S, Tucker W, Sanderson C, Hapel A, Campbell H, Young I . Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene. Nature. 1985; 317(6034):255-8. DOI: 10.1038/317255a0. View

Hart C, Awgulewitsch A, Fainsod A, McGinnis W, Ruddle F . Homeo box gene complex on mouse chromosome 11: molecular cloning, expression in embryogenesis, and homology to a human homeo box locus. Cell. 1985; 43(1):9-18. DOI: 10.1016/0092-8674(85)90007-8. View

Hapel A, Vande Woude G, Campbell H, Young I, Robins T . Generation of an autocrine leukaemia using a retroviral expression vector carrying the interleukin-3 gene. Lymphokine Res. 1986; 5(4):249-54. View

10.

Bowtell D, Johnson G, Kelso A, Cory S . Expression of genes transferred to haemopoietic stem cells by recombinant retroviruses. Mol Biol Med. 1987; 4(4):229-50. View

11.

Beug H, Blundell P, Graf T . Reversibility of differentiation and proliferative capacity in avian myelomonocytic cells transformed by tsE26 leukemia virus. Genes Dev. 1987; 1(3):277-86. DOI: 10.1101/gad.1.3.277. View

12.

Takebe Y, Seiki M, Fujisawa J, Hoy P, Yokota K, Arai K . SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988; 8(1):466-72. PMC: 363152. DOI: 10.1128/mcb.8.1.466-472.1988. View

13.

Spangrude G, Heimfeld S, Weissman I . Purification and characterization of mouse hematopoietic stem cells. Science. 1988; 241(4861):58-62. DOI: 10.1126/science.2898810. View

14.

Morishita K, Parker D, Mucenski M, Jenkins N, Copeland N, Ihle J . Retroviral activation of a novel gene encoding a zinc finger protein in IL-3-dependent myeloid leukemia cell lines. Cell. 1988; 54(6):831-40. DOI: 10.1016/s0092-8674(88)91175-0. View

15.

Kongsuwan K, Webb E, Housiaux P, Adams J . Expression of multiple homeobox genes within diverse mammalian haemopoietic lineages. EMBO J. 1988; 7(7):2131-8. PMC: 454515. DOI: 10.1002/j.1460-2075.1988.tb03052.x. View

16.

Xu W, GORMAN P, Rider S, Hedge P, Moore G, Prichard C . Construction of a genetic map of human chromosome 17 by use of chromosome-mediated gene transfer. Proc Natl Acad Sci U S A. 1988; 85(22):8563-7. PMC: 282499. DOI: 10.1073/pnas.85.22.8563. View

17.

Langdon W, Harris A, Cory S . Growth of E mu-myc transgenic B-lymphoid cells in vitro and their evolution toward autonomy. Oncogene Res. 1988; 3(3):271-9. View

18.

Holland P, Hogan B . Expression of homeo box genes during mouse development: a review. Genes Dev. 1988; 2(7):773-82. DOI: 10.1101/gad.2.7.773. View

19.

Herr W, Sturm R, Clerc R, Corcoran L, Baltimore D, Sharp P . The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev. 1988; 2(12A):1513-6. DOI: 10.1101/gad.2.12a.1513. View

20.

Kongsuwan K, Allen J, Adams J . Expression of Hox-2.4 homeobox gene directed by proviral insertion in a myeloid leukemia. Nucleic Acids Res. 1989; 17(5):1881-92. PMC: 317530. DOI: 10.1093/nar/17.5.1881. View