Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1993 Jan;13(1):351–357. doi: 10.1128/mcb.13.1.351

E2A-Pbx1, the t(1;19) translocation protein of human pre-B-cell acute lymphocytic leukemia, causes acute myeloid leukemia in mice.

M P Kamps 1, D Baltimore 1
PMCID: PMC358914  PMID: 8093327

Abstract

One-quarter of pediatric pre-B-cell leukemias contain the t(1;19) chromosomal translocation, which fuses 5' exons encoding the transactivation domain of the E2A transcription factor gene to 3' exons ecoding the putative DNA-binding region of the unusual homeobox gene, PBX1. To test the leukemic potential of this fused gene, a cDNA encoding its major protein product, p85E2A-Pbx1, was incorporated into a retrovirus construct and introduced into normal mouse marrow progenitors by infection. The cells were used in a bone marrow transplantation protocol to reconstitute the hematopoietic compartments of lethally irradiated recipients. After 3 to 8 months, reconstituted mice developed acute myeloid leukemias that expressed high levels of p85E2A-Pbx1 and were readily transmissible to immunocompetent mice. Most acute myeloid leukemias also grew as granulocytic sarcomas and exhibited some neutrophilic differentiation. These results demonstrate a causative role for p85E2A-Pbx1 in human acute leukemia and indicate that the oncogenic potential of Pbx1 is not limited to pre-B-cell malignancies.

Full text

PDF
351

Images in this article

354Image
on p.354
356Image
on p.356

Selected References

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

  1. Bos J. L., Verlaan-de Vries M., van der Eb A. J., Janssen J. W., Delwel R., Löwenberg B., Colly L. P. Mutations in N-ras predominate in acute myeloid leukemia. Blood. 1987 Apr;69(4):1237–1241. [PubMed] [Google Scholar]
  2. Carroll A. J., Crist W. M., Parmley R. T., Roper M., Cooper M. D., Finley W. H. Pre-B cell leukemia associated with chromosome translocation 1;19. Blood. 1984 Mar;63(3):721–724. [PubMed] [Google Scholar]
  3. Catalano M. F., Levin B., Hart R. S., Troncoso P., DuBrow R. A., Estey E. H. Granulocytic sarcoma of the colon. Gastroenterology. 1991 Feb;100(2):555–559. doi: 10.1016/0016-5085(91)90230-i. [DOI] [PubMed] [Google Scholar]
  4. Cook W. D., Metcalf D., Nicola N. A., Burgess A. W., Walker F. Malignant transformation of a growth factor-dependent myeloid cell line by Abelson virus without evidence of an autocrine mechanism. Cell. 1985 Jul;41(3):677–683. doi: 10.1016/s0092-8674(85)80048-9. [DOI] [PubMed] [Google Scholar]
  5. Daley G. Q., Baltimore D. Transformation of an interleukin 3-dependent hematopoietic cell line by the chronic myelogenous leukemia-specific P210bcr/abl protein. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9312–9316. doi: 10.1073/pnas.85.23.9312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Daley G. Q., Van Etten R. A., Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990 Feb 16;247(4944):824–830. doi: 10.1126/science.2406902. [DOI] [PubMed] [Google Scholar]
  7. Doshi H. M., Schochet S. S., Jr, Gold M., Nugent G. R. Granulocytic sarcoma presenting as an epidural mass with acute paraparesis in an aleukemic patient. Am J Clin Pathol. 1991 Feb;95(2):228–232. doi: 10.1093/ajcp/95.2.228. [DOI] [PubMed] [Google Scholar]
  8. Heard J. M., Roussel M. F., Rettenmier C. W., Sherr C. J. Multilineage hematopoietic disorders induced by transplantation of bone marrow cells expressing the v-fms oncogene. Cell. 1987 Nov 20;51(4):663–673. doi: 10.1016/0092-8674(87)90135-8. [DOI] [PubMed] [Google Scholar]
  9. Henthorn P., Kiledjian M., Kadesch T. Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. Science. 1990 Jan 26;247(4941):467–470. doi: 10.1126/science.2105528. [DOI] [PubMed] [Google Scholar]
  10. Kamps M. P., Look A. T., Baltimore D. The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials. Genes Dev. 1991 Mar;5(3):358–368. doi: 10.1101/gad.5.3.358. [DOI] [PubMed] [Google Scholar]
  11. Kamps M. P., Murre C., Sun X. H., Baltimore D. A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL. Cell. 1990 Feb 23;60(4):547–555. doi: 10.1016/0092-8674(90)90658-2. [DOI] [PubMed] [Google Scholar]
  12. Meis J. M., Butler J. J., Osborne B. M., Manning J. T. Granulocytic sarcoma in nonleukemic patients. Cancer. 1986 Dec 15;58(12):2697–2709. doi: 10.1002/1097-0142(19861215)58:12<2697::aid-cncr2820581225>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  13. Monica K., Galili N., Nourse J., Saltman D., Cleary M. L. PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1. Mol Cell Biol. 1991 Dec;11(12):6149–6157. doi: 10.1128/mcb.11.12.6149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mosch A., Kuiters R. R., Kazzaz B. A. Intradural granulocytic sarcoma: a rare cause of sciatic pain. Clin Neurol Neurosurg. 1991;93(4):341–344. doi: 10.1016/0303-8467(91)90103-v. [DOI] [PubMed] [Google Scholar]
  15. Neiman R. S., Barcos M., Berard C., Bonner H., Mann R., Rydell R. E., Bennett J. M. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer. 1981 Sep 15;48(6):1426–1437. doi: 10.1002/1097-0142(19810915)48:6<1426::aid-cncr2820480626>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  16. Nourse J., Mellentin J. D., Galili N., Wilkinson J., Stanbridge E., Smith S. D., Cleary M. L. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell. 1990 Feb 23;60(4):535–545. doi: 10.1016/0092-8674(90)90657-z. [DOI] [PubMed] [Google Scholar]
  17. Palacios R., Karasuyama H., Rolink A. Ly1+ PRO-B lymphocyte clones. Phenotype, growth requirements and differentiation in vitro and in vivo. EMBO J. 1987 Dec 1;6(12):3687–3693. doi: 10.1002/j.1460-2075.1987.tb02702.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rodenhuis S., Bos J. L., Slater R. M., Behrendt H., van 't Veer M., Smets L. A. Absence of oncogene amplifications and occasional activation of N-ras in lymphoblastic leukemia of childhood. Blood. 1986 Jun;67(6):1698–1704. [PubMed] [Google Scholar]
  19. Takemori N., Hirai K., Onodera R., Saito N., Tachibana N., Uenishi H., Takasugi Y., Namiki M. Granulocytic sarcoma of the submandibular lymph node preceding overt leukemia: significance of strict evaluation of bone marrow. Am J Clin Pathol. 1991 Nov;96(5):675–677. doi: 10.1093/ajcp/96.5.675. [DOI] [PubMed] [Google Scholar]
  20. Whitlock C. A., Witte O. N. Abelson virus-infected cells can exhibit restricted in vitro growth and low oncogenic potential. J Virol. 1981 Nov;40(2):577–584. doi: 10.1128/jvi.40.2.577-584.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Williams D. L., Look A. T., Melvin S. L., Roberson P. K., Dahl G., Flake T., Stass S. New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia. Cell. 1984 Jan;36(1):101–109. doi: 10.1016/0092-8674(84)90078-3. [DOI] [PubMed] [Google Scholar]
  22. Wodzinski M. A., Collin R., Winfield D. A., Dalton A., Lawrence A. C. Epidural granulocytic sarcoma in acute myeloid leukemia with 8;21 translocation. Cancer. 1988 Oct 1;62(7):1299–1300. doi: 10.1002/1097-0142(19881001)62:7<1299::aid-cncr2820620709>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  23. Yamamoto K., Akiyama H., Maruyama T., Sakamaki H., Onozawa Y., Kawaguchi K. Granulocytic sarcoma of the ovary in patients with acute myelogenous leukemia. Am J Hematol. 1991 Nov;38(3):223–225. doi: 10.1002/ajh.2830380313. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES