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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 May;85(10):3590–3594. doi: 10.1073/pnas.85.10.3590

Prognostic significance of "short-term" effects of chemotherapy on MYC and histone H3 mRNA levels in acute leukemia patients.

D Venturelli 1, B Lange 1, F Narni 1, L Selleri 1, M T Mariano 1, U Torelli 1, A M Gewirtz 1, B Calabretta 1
PMCID: PMC280259  PMID: 3285345

Abstract

We have found that administration of chemotherapy alters expression of growth-regulated genes in leukemia blast cells. To determine if such changes might be correlated with therapeutic outcome, we studied steady-state mRNA levels of MYC and histone H3 in the leukemic blasts of patients just prior to and 24 hr after the administration of the first doses of antileukemic drug therapy. Among nine patients with acute myelogenous leukemia, mRNA levels of MYC and histone H3 were reduced in five patients, and hematologic remission was achieved in three of these individuals. No remission was obtained in the four patients without reduction in MYC and histone H3 mRNA. Among acute lymphocytic leukemia patients, the mRNA levels of MYC and/or histone H3 were reduced by the therapy in seven of nine patients. A complete hematologic remission was obtained in five of them, and a partial remission was obtained in the other two. No remission was obtained in the patients in which MYC and H3 mRNA levels were unaffected by the therapy. These studies are of interest because they suggest that a decrease in the mRNA levels of MYC and histone H3 24 hr after a single dose of antineoplastic drugs may predict which patients will achieve complete remission; lack of reduction in these mRNAs correlates with failure to achieve remission. In addition, these studies also provide further proof of the heterogeneity of altered growth regulation among human leukemias.

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  1. Bennett J. M., Catovsky D., Daniel M. T., Flandrin G., Galton D. A., Gralnick H. R., Sultan C. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976 Aug;33(4):451–458. doi: 10.1111/j.1365-2141.1976.tb03563.x. [DOI] [PubMed] [Google Scholar]
  2. Calabretta B., Kaczmarek L., Mars W., Ochoa D., Gibson C. W., Hirschhorn R. R., Baserga R. Cell-cycle-specific genes differentially expressed in human leukemias. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4463–4467. doi: 10.1073/pnas.82.13.4463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Calabretta B., Venturelli D., Kaczmarek L., Narni F., Talpaz M., Anderson B., Beran M., Baserga R. Altered expression of G1-specific genes in human malignant myeloid cells. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1495–1498. doi: 10.1073/pnas.83.5.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dalla-Favera R., Gelmann E. P., Martinotti S., Franchini G., Papas T. S., Gallo R. C., Wong-Staal F. Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A. 1982 Nov;79(21):6497–6501. doi: 10.1073/pnas.79.21.6497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dani C., Blanchard J. M., Piechaczyk M., El Sabouty S., Marty L., Jeanteur P. Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7046–7050. doi: 10.1073/pnas.81.22.7046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Elder P. K., Schmidt L. J., Ono T., Getz M. J. Specific stimulation of actin gene transcription by epidermal growth factor and cycloheximide. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7476–7480. doi: 10.1073/pnas.81.23.7476. [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. Ferrari S., Narni F., Mars W., Kaczmarek L., Venturelli D., Anderson B., Calabretta B. Expression of growth-regulated genes in human acute leukemias. Cancer Res. 1986 Oct;46(10):5162–5166. [PubMed] [Google Scholar]
  9. Frazier M. L., Mars W., Florine D. L., Montagna R. A., Saunders G. F. Efficient extraction of RNA from mammalian tissue. Mol Cell Biochem. 1983;56(2):113–122. doi: 10.1007/BF00227211. [DOI] [PubMed] [Google Scholar]
  10. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  11. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  12. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heintz N., Sive H. L., Roeder R. G. Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle. Mol Cell Biol. 1983 Apr;3(4):539–550. doi: 10.1128/mcb.3.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kaczmarek L., Calabretta B., Baserga R. Expression of cell-cycle-dependent genes in phytohemagglutinin-stimulated human lymphocytes. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5375–5379. doi: 10.1073/pnas.82.16.5375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
  16. Khalili K., Weinmann R. Actin mRNAs in HeLa cells. Stabilization after adenovirus infection. J Mol Biol. 1984 Dec 25;180(4):1007–1021. doi: 10.1016/0022-2836(84)90268-7. [DOI] [PubMed] [Google Scholar]
  17. Plumb M., Stein J., Stein G. Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells. Nucleic Acids Res. 1983 Apr 25;11(8):2391–2410. doi: 10.1093/nar/11.8.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  19. Rothberg P. G., Erisman M. D., Diehl R. E., Rovigatti U. G., Astrin S. M. Structure and expression of the oncogene c-myc in fresh tumor material from patients with hematopoietic malignancies. Mol Cell Biol. 1984 Jun;4(6):1096–1103. doi: 10.1128/mcb.4.6.1096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  21. Suggs S. V., Wallace R. B., Hirose T., Kawashima E. H., Itakura K. Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6613–6617. doi: 10.1073/pnas.78.11.6613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Thompson C. B., Challoner P. B., Neiman P. E., Groudine M. Levels of c-myc oncogene mRNA are invariant throughout the cell cycle. 1985 Mar 28-Apr 3Nature. 314(6009):363–366. doi: 10.1038/314363a0. [DOI] [PubMed] [Google Scholar]
  24. Torelli U., Selleri L., Venturelli D., Donelli A., Emilia G., Ceccherelli G., Turchi L., Torelli G. Differential patterns of expression of cell cycle-related genes in blast cells of acute myeloid leukemia. Leuk Res. 1986;10(10):1249–1254. doi: 10.1016/0145-2126(86)90244-4. [DOI] [PubMed] [Google Scholar]
  25. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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