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. 1987 Aug;84(16):5913–5917. doi: 10.1073/pnas.84.16.5913

The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q.

M M Le Beau, N D Epstein, S J O'Brien, A W Nienhuis, Y C Yang, S C Clark, J D Rowley
PMCID: PMC298973  PMID: 3497400

Abstract

The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, we localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33 [del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent form the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF (the gene encoding granulocyte-macrophage-CSF), CSF-1 (the gene encoding macrophage-CSF), and FMS (the human c-fms protooncogene, which encodes the CSF-1 receptor). Our findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q-chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).

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Selected References

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  1. Dewald G. W., Davis M. P., Pierre R. V., O'Fallon J. R., Hoagland H. C. Clinical characteristics and prognosis of 50 patients with a myeloproliferative syndrome and deletion of part of the long arm of chromosome 5. Blood. 1985 Jul;66(1):189–197. [PubMed] [Google Scholar]
  2. Friend S. H., Bernards R., Rogelj S., Weinberg R. A., Rapaport J. M., Albert D. M., Dryja T. P. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. doi: 10.1038/323643a0. [DOI] [PubMed] [Google Scholar]
  3. Groffen J., Stephenson J. R., Heisterkamp N., de Klein A., Bartram C. R., Grosveld G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell. 1984 Jan;36(1):93–99. doi: 10.1016/0092-8674(84)90077-1. [DOI] [PubMed] [Google Scholar]
  4. Huebner K., Isobe M., Croce C. M., Golde D. W., Kaufman S. E., Gasson J. C. The human gene encoding GM-CSF is at 5q21-q32, the chromosome region deleted in the 5q- anomaly. Science. 1985 Dec 13;230(4731):1282–1285. doi: 10.1126/science.2999978. [DOI] [PubMed] [Google Scholar]
  5. Kawasaki E. S., Ladner M. B., Wang A. M., Van Arsdell J., Warren M. K., Coyne M. Y., Schweickart V. L., Lee M. T., Wilson K. J., Boosman A. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science. 1985 Oct 18;230(4723):291–296. doi: 10.1126/science.2996129. [DOI] [PubMed] [Google Scholar]
  6. Lang R. A., Metcalf D., Gough N. M., Dunn A. R., Gonda T. J. Expression of a hemopoietic growth factor cDNA in a factor-dependent cell line results in autonomous growth and tumorigenicity. Cell. 1985 Dec;43(2 Pt 1):531–542. doi: 10.1016/0092-8674(85)90182-5. [DOI] [PubMed] [Google Scholar]
  7. Le Beau M. M., Albain K. S., Larson R. A., Vardiman J. W., Davis E. M., Blough R. R., Golomb H. M., Rowley J. D. Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7. J Clin Oncol. 1986 Mar;4(3):325–345. doi: 10.1200/JCO.1986.4.3.325. [DOI] [PubMed] [Google Scholar]
  8. Le Beau M. M., Westbrook C. A., Diaz M. O., Larson R. A., Rowley J. D., Gasson J. C., Golde D. W., Sherr C. J. Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders. Science. 1986 Feb 28;231(4741):984–987. doi: 10.1126/science.3484837. [DOI] [PubMed] [Google Scholar]
  9. Le Beau M. M., Westbrook C. A., Diaz M. O., Rowley J. D. Evidence for two distinct c-src loci on human chromosomes 1 and 20. Nature. 1984 Nov 1;312(5989):70–71. doi: 10.1038/312070a0. [DOI] [PubMed] [Google Scholar]
  10. Metcalf D. The granulocyte-macrophage colony-stimulating factors. Science. 1985 Jul 5;229(4708):16–22. doi: 10.1126/science.2990035. [DOI] [PubMed] [Google Scholar]
  11. Murphree A. L., Benedict W. F. Retinoblastoma: clues to human oncogenesis. Science. 1984 Mar 9;223(4640):1028–1033. doi: 10.1126/science.6320372. [DOI] [PubMed] [Google Scholar]
  12. Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. 1986 Jan 30-Feb 5Nature. 319(6052):415–418. doi: 10.1038/319415a0. [DOI] [PubMed] [Google Scholar]
  13. Nienhuis A. W., Bunn H. F., Turner P. H., Gopal T. V., Nash W. G., O'Brien S. J., Sherr C. J. Expression of the human c-fms proto-oncogene in hematopoietic cells and its deletion in the 5q- syndrome. Cell. 1985 Sep;42(2):421–428. doi: 10.1016/0092-8674(85)90099-6. [DOI] [PubMed] [Google Scholar]
  14. O'Brien S. J., Bonner T. I., Cohen M., O'Connell C., Nash W. G. Mapping of an endogenous retroviral sequence to human chromosome 18. Nature. 1983 May 5;303(5912):74–77. doi: 10.1038/303074a0. [DOI] [PubMed] [Google Scholar]
  15. O'Brien S. J., Nash W. G., Goodwin J. L., Lowy D. R., Chang E. H. Dispersion of the ras family of transforming genes to four different chromosomes in man. Nature. 1983 Apr 28;302(5911):839–842. doi: 10.1038/302839a0. [DOI] [PubMed] [Google Scholar]
  16. Pedersen-Bjergaard J., Philip P., Pedersen N. T., Hou-Jensen K., Svejgaard A., Jensen G., Nissen N. I. Acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome secondary to treatment of other malignant diseases. II. Bone marrow cytology, cytogenetics, results of HLA typing, response to antileukemic chemotherapy, and survival in a total series of 55 patients. Cancer. 1984 Aug 1;54(3):452–462. doi: 10.1002/1097-0142(19840801)54:3<452::aid-cncr2820540313>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  17. Pettenati M. J., Le Beau M. M., Lemons R. S., Shima E. A., Kawasaki E. S., Larson R. A., Sherr C. J., Diaz M. O., Rowley J. D. Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders. Proc Natl Acad Sci U S A. 1987 May;84(9):2970–2974. doi: 10.1073/pnas.84.9.2970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rowley J. D., Golomb H. M., Vardiman J. W. Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease. Blood. 1981 Oct;58(4):759–767. [PubMed] [Google Scholar]
  19. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  20. Sieff C. A., Emerson S. G., Donahue R. E., Nathan D. G., Wang E. A., Wong G. G., Clark S. C. Human recombinant granulocyte-macrophage colony-stimulating factor: a multilineage hematopoietin. Science. 1985 Dec 6;230(4730):1171–1173. doi: 10.1126/science.3877981. [DOI] [PubMed] [Google Scholar]
  21. Souza L. M., Boone T. C., Gabrilove J., Lai P. H., Zsebo K. M., Murdock D. C., Chazin V. R., Bruszewski J., Lu H., Chen K. K. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science. 1986 Apr 4;232(4746):61–65. doi: 10.1126/science.2420009. [DOI] [PubMed] [Google Scholar]
  22. Tomonaga M., Golde D. W., Gasson J. C. Biosynthetic (recombinant) human granulocyte-macrophage colony-stimulating factor: effect on normal bone marrow and leukemia cell lines. Blood. 1986 Jan;67(1):31–36. [PubMed] [Google Scholar]
  23. Van den Berghe H., Cassiman J. J., David G., Fryns J. P., Michaux J. L., Sokal G. Distinct haematological disorder with deletion of long arm of no. 5 chromosome. Nature. 1974 Oct 4;251(5474):437–438. doi: 10.1038/251437a0. [DOI] [PubMed] [Google Scholar]
  24. Van den Berghe H., Vermaelen K., Mecucci C., Barbieri D., Tricot G. The 5q-anomaly. Cancer Genet Cytogenet. 1985 Jul;17(3):189–255. doi: 10.1016/0165-4608(85)90016-0. [DOI] [PubMed] [Google Scholar]
  25. Wheeler E. F., Rettenmier C. W., Look A. T., Sherr C. J. The v-fms oncogene induces factor independence and tumorigenicity in CSF-1 dependent macrophage cell line. 1986 Nov 27-Dec 3Nature. 324(6095):377–380. doi: 10.1038/324377a0. [DOI] [PubMed] [Google Scholar]
  26. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
  27. Wong P. M., Chung S. W., Nienhuis A. W. Retroviral transfer and expression of the interleukin-3 gene in hemopoietic cells. Genes Dev. 1987 Jun;1(4):358–365. doi: 10.1101/gad.1.4.358. [DOI] [PubMed] [Google Scholar]
  28. Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]
  29. Yarden Y., Escobedo J. A., Kuang W. J., Yang-Feng T. L., Daniel T. O., Tremble P. M., Chen E. Y., Ando M. E., Harkins R. N., Francke U. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. Nature. 1986 Sep 18;323(6085):226–232. doi: 10.1038/323226a0. [DOI] [PubMed] [Google Scholar]
  30. Young D. C., Griffin J. D. Autocrine secretion of GM-CSF in acute myeloblastic leukemia. Blood. 1986 Nov;68(5):1178–1181. [PubMed] [Google Scholar]

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