Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1992 Mar;11(3):983–989. doi: 10.1002/j.1460-2075.1992.tb05137.x

Modulation of homeobox gene expression alters the phenotype of human hematopoietic cell lines.

W F Shen 1, K Detmer 1, C H Mathews 1, F M Hack 1, D A Morgan 1, C Largman 1, H J Lawrence 1
PMCID: PMC556539  PMID: 1372255

Abstract

We have previously reported that certain genes of the HOX2 cluster of homeobox genes on human chromosome 17 are specifically expressed in human leukemic cell lines with erythroid potential, suggesting that these genes are involved in hematopoietic differentiation. We now show that the expression of the HOX 2.2 gene decreases during erythropoietin-induced differentiation of the erythroid cell line MB02. In order to study the role of the HOX 2.2 homeobox gene in hematopoiesis, vectors producing sense or antisense transcripts were introduced into K562 and HEL cells, pluripotent lines with erythroid and myeloid features. Overexpression of HOX 2.2 is associated with loss of erythroid features in both lines and an increase in certain myelomonocytic markers in K562 cells. Expression of antisense HOX 2.2 is associated with an increase in erythroid features in HEL cells and a mild decrease in myeloid characteristics in K562 cells. Overexpression of the adjacent HOX 2.1 gene in K562 cells does not produce similar phenotype changes. These data demonstrate that modulation of a specific HOX 2 homeobox gene can change the phenotype of somatic cells and suggest that certain HOX 2 genes play a role in blood cell differentiation.

Full text

PDF
983

Images in this article

984Image
on p.984
984Image
on p.984
985Image
on p.985
986Image
on p.986
988Image
on p.988

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akam M. Hox and HOM: homologous gene clusters in insects and vertebrates. Cell. 1989 May 5;57(3):347–349. doi: 10.1016/0092-8674(89)90909-4. [DOI] [PubMed] [Google Scholar]
  2. Balling R., Mutter G., Gruss P., Kessel M. Craniofacial abnormalities induced by ectopic expression of the homeobox gene Hox-1.1 in transgenic mice. Cell. 1989 Jul 28;58(2):337–347. doi: 10.1016/0092-8674(89)90848-9. [DOI] [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Chisaka O., Capecchi M. R. Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature. 1991 Apr 11;350(6318):473–479. doi: 10.1038/350473a0. [DOI] [PubMed] [Google Scholar]
  5. Clarke B. J., Brickenden A. M., Ives R. A., Chui D. H. Effect of modulators of erythropoiesis on the hemoglobinization of human erythroid cell cultures. Blood. 1982 Aug;60(2):346–351. [PubMed] [Google Scholar]
  6. Duboule D., Dollé P. The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO J. 1989 May;8(5):1497–1505. doi: 10.1002/j.1460-2075.1989.tb03534.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  8. Gehring W. J. Homeo boxes in the study of development. Science. 1987 Jun 5;236(4806):1245–1252. doi: 10.1126/science.2884726. [DOI] [PubMed] [Google Scholar]
  9. Graham A., Papalopulu N., Krumlauf R. The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell. 1989 May 5;57(3):367–378. doi: 10.1016/0092-8674(89)90912-4. [DOI] [PubMed] [Google Scholar]
  10. Hauer C. A., Getty R. R., Tykocinski M. L. Epstein-Barr virus episome-based promoter function in human myeloid cells. Nucleic Acids Res. 1989 Mar 11;17(5):1989–2003. doi: 10.1093/nar/17.5.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kongsuwan K., Webb E., Housiaux P., Adams J. M. Expression of multiple homeobox genes within diverse mammalian haemopoietic lineages. EMBO J. 1988 Jul;7(7):2131–2138. doi: 10.1002/j.1460-2075.1988.tb03052.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lavelle D., Ducksworth J., Eves E., Gomes G., Keller M., Heller P., DeSimone J. A homeodomain protein binds to gamma-globin gene regulatory sequences. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7318–7322. doi: 10.1073/pnas.88.16.7318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Levine M., Hoey T. Homeobox proteins as sequence-specific transcription factors. Cell. 1988 Nov 18;55(4):537–540. doi: 10.1016/0092-8674(88)90209-7. [DOI] [PubMed] [Google Scholar]
  14. Lowney P., Corral J., Detmer K., LeBeau M. M., Deaven L., Lawrence H. J., Largman C. A human Hox 1 homeobox gene exhibits myeloid-specific expression of alternative transcripts in human hematopoietic cells. Nucleic Acids Res. 1991 Jun 25;19(12):3443–3449. doi: 10.1093/nar/19.12.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lozzio B. B., Lozzio C. B., Bamberger E. G., Feliu A. S. A multipotential leukemia cell line (K-562) of human origin. Proc Soc Exp Biol Med. 1981 Apr;166(4):546–550. doi: 10.3181/00379727-166-41106. [DOI] [PubMed] [Google Scholar]
  16. Martin P., Papayannopoulou T. HEL cells: a new human erythroleukemia cell line with spontaneous and induced globin expression. Science. 1982 Jun 11;216(4551):1233–1235. doi: 10.1126/science.6177045. [DOI] [PubMed] [Google Scholar]
  17. Mathews C. H., Detmer K., Boncinelli E., Lawrence H. J., Largman C. Erythroid-restricted expression of homeobox genes of the human HOX 2 locus. Blood. 1991 Nov 1;78(9):2248–2252. [PubMed] [Google Scholar]
  18. McNally M. A., Lebkowski J. S., Okarma T. B., Lerch L. B. Optimizing electroporation parameters for a variety of human hematopoietic cell lines. Biotechniques. 1988 Oct;6(9):882–886. [PubMed] [Google Scholar]
  19. Metcalf D. The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature. 1989 May 4;339(6219):27–30. doi: 10.1038/339027a0. [DOI] [PubMed] [Google Scholar]
  20. Papayannopoulou T., Nakamoto B., Kurachi S., Nelson R. Analysis of the erythroid phenotype of HEL cells: clonal variation and the effect of inducers. Blood. 1987 Dec;70(6):1764–1772. [PubMed] [Google Scholar]
  21. Rowley P. T., Ohlsson-Wilhelm B. M., Farley B. A. K562 human erythroleukemia cells demonstrate commitment. Blood. 1985 Apr;65(4):862–868. [PubMed] [Google Scholar]
  22. Shen W. F., Largman C., Lowney P., Corral J. C., Detmer K., Hauser C. A., Simonitch T. A., Hack F. M., Lawrence H. J. Lineage-restricted expression of homeobox-containing genes in human hematopoietic cell lines. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8536–8540. doi: 10.1073/pnas.86.21.8536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shen W. F., Largman C., Lowney P., Hack F. M., Lawrence H. J. Expression of homeobox genes in human erythroleukemia cells. Adv Exp Med Biol. 1989;271:211–219. doi: 10.1007/978-1-4613-0623-8_22. [DOI] [PubMed] [Google Scholar]
  24. Takeda K., Minowada J., Bloch A. Kinetics of appearance of differentiation-associated characteristics in ML-1, a line of human myeloblastic leukemia cells, after treatment with 12-O-tetradecanoylphorbol-13-acetate, dimethyl sulfoxide or 1-beta-D-arabinofuranosylcytosine. Cancer Res. 1982 Dec;42(12):5152–5158. [PubMed] [Google Scholar]
  25. Tsai S. F., Martin D. I., Zon L. I., D'Andrea A. D., Wong G. G., Orkin S. H. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature. 1989 Jun 8;339(6224):446–451. doi: 10.1038/339446a0. [DOI] [PubMed] [Google Scholar]
  26. Wolgemuth D. J., Behringer R. R., Mostoller M. P., Brinster R. L., Palmiter R. D. Transgenic mice overexpressing the mouse homoeobox-containing gene Hox-1.4 exhibit abnormal gut development. Nature. 1989 Feb 2;337(6206):464–467. doi: 10.1038/337464a0. [DOI] [PubMed] [Google Scholar]
  27. Yates J. L., Warren N., Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. 1985 Feb 28-Mar 6Nature. 313(6005):812–815. doi: 10.1038/313812a0. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES