Medical Oncology

, Volume 12, Issue 3, pp 157–166 | Cite as

Molecular biology of leukemia for the clinician

  • Elisabeth Paietta


Although significant progress has been made in the treatment of the acute leukemias, therapies are generally non-specific and not targeted at the biologic defects underlying these diseases. Consequently, treatment results are suboptimal. The development of leukemic cell phenotype-specific therapies is hampered by our limited knowledge of the biology of acute leukemias. That characterizing the genetic defect may revolutionize treatment approach and disease outcome has recently been proven in acute promyelocytic leukemia. Once identified, genes involved in the pathogenesis of leukemic subtypes not only allow for improved diagnosis and monitoring of minimal residual leukemic cells but may ultimately lead to the development of innovative drug strategies that aim at the inhibition of disease-related genes or their encoded proteins. The focus of this review is to familiarize the practicing physician with some principles of molecular biology and with its current and future goals with respect to leukemia.


Leukemia molecular biology 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rabbitts, T.H. (1991) Translocations, master genes, and differences between the origins of acute and chronic leukemias.Cell 67, 641.PubMedCrossRefGoogle Scholar
  2. 2.
    Cline, M.J. (1994) The molecular basis of leukemia.New Engl. J. Med. 330, 328.PubMedCrossRefGoogle Scholar
  3. 3.
    Biedler, J.L. (1994) Drug resistance: Genotype versus phenotype — Thirty-second G.H.A. Clowes Memorial Award Lecture.Cancer Res. 54, 666.PubMedGoogle Scholar
  4. 4.
    Gottesman, M. (1993) How cancer cells evade chemotherapy: Sixteenth Richard and Hinda Rosenthal Foundation Award Lecture.Cancer Res. 53, 747.PubMedGoogle Scholar
  5. 5.
    Arceci, R. (1993) Clinical significance of P-glycoprotein in multidrug resistance malignancies.Blood 81, 2215.PubMedGoogle Scholar
  6. 6.
    Simon, S.M. and Schindler, M. (1994) Cell biological mechanisms of multidrug resistance in tumors.Proc. Natl. Acad. Sci. USA 91, 3497.PubMedCrossRefGoogle Scholar
  7. 7.
    Paietta, E. (1995) Immunobiology of acute leukemia. In: P.H. Wiernik, G.P. Canellos, R.A. Kyle and J.P. Dutcher (eds)Neoplastic Diseases of the Blood, 3rd Edn, New York: Churchill Livingston (in press).Google Scholar
  8. 8.
    Chaudhary, P.M. and Roninson, I.B. (1993) Induction of multidrug resistance in human cells by transient exposure to different chemotherapeutic drugs.J. Natl. Cancer Inst. 85, 632.PubMedCrossRefGoogle Scholar
  9. 9.
    Nooter, K. and Sonneveld, P. (1994) Clinical relevance of P-glycoprotein expression in haematological malignancies.Leukemia Res. 18, 233.CrossRefGoogle Scholar
  10. 10.
    Paietta, E., Andersen, J., Rowe, J., Cassileth, P. and Wiernik, P.H. (1995) Myeloid blast cell maturation determines response in adult de novo acute myeloid leukemia (AML): A response-driven antigen expression analysis in 382 Eastern Cooperative Oncology Group (ECOG) patients.Proc. Am. Soc. Clin. Oncol. (in press).Google Scholar
  11. 11.
    Paietta, E., Andersen, J., Racevskis, J., Ashigbi, M., Cassileth, P. and Wiernik, P.H. (1995) Modulation of multidrug resistance inde novo adult acute myeloid leukemia: Variable efficacy of reverting agentsin vitro. Blood Rev. (in press).Google Scholar
  12. 12.
    Kellen, J.A. (1993) The reversal of multidrug resistance in cancer.Anticancer Res. 13, 959.PubMedGoogle Scholar
  13. 13.
    Sikic, B.I. (1993) Modulation of multidrug resistance: At the threshold.J. Clin. Oncol. 11, 1629.PubMedGoogle Scholar
  14. 14.
    Croce, C.M. (1986) Chromosome translocations and human cancer.Cancer Res. 46, 6019.PubMedGoogle Scholar
  15. 15.
    Evans, H.J. (1993) Molecular genetic aspects of human cancers: The 1993 Frank Rose Lecture.Br. J. Cancer 68, 1051.PubMedGoogle Scholar
  16. 16.
    Morgan, G.J., Shiach, C. and Potter, M. (1994) The clinical value of detecting gene rearrangements in acute leukemias.Br. J. Haematol. 88, 459.PubMedCrossRefGoogle Scholar
  17. 17.
    Cantley, L.C., Auger, K.R., Carpenter, C., Duckworth, B., Graziani, A., Kapeller, R. and Soltoff, S. (1991) Oncogenes and signal transduction.Cell 64, 281.PubMedCrossRefGoogle Scholar
  18. 18.
    Lawrence, H.J. and Largman, C. (1992) Homeobox genes in normal hematopoiesis and leukemia.Blood 80, 2445.PubMedGoogle Scholar
  19. 19.
    Nichols, J. and Nimer, S.D. (1992) Transcription factors, translocations, and leukemia.Blood 80, 2953.PubMedGoogle Scholar
  20. 20.
    Sachs, L. and Lotem, J. (1993) Control of programmed cell death in normal and leukemic cells: New implications for therapy.Blood 82, 15.PubMedGoogle Scholar
  21. 21.
    Kerr, J.F.R., Winterford, C.M. and Harmon, B.V. (1994) Apoptosis. Its significance in cancer and cancer therapy.Cancer 73, 2013.PubMedCrossRefGoogle Scholar
  22. 22.
    Cowell, J.K. (1992) Tumor suppressor genes.Ann. Oncol. 3, 693.PubMedGoogle Scholar
  23. 23.
    Knudson, A.G. (1993) Antioncogenes and human cancer.Proc. Natl. Acad. Sci. USA 90, 10914.PubMedCrossRefGoogle Scholar
  24. 24.
    Bash, R.O., Smith, R.G. and Baer, R. (1994) The TAL1 proto-oncogene: A critical mediator of T-cell acute lymphoblastic leukemia?Clin. Immunol. Newslett. 14, 33.CrossRefGoogle Scholar
  25. 25.
    McGuire, E.A. (1994) Ttg-1: A paradigm for transcription factor deregulation in T-ALL.Clin. Immunol. Newslett. 14, 48.CrossRefGoogle Scholar
  26. 26.
    Frankel, S.R. (1993) Acute promyelocytic leukemia. New insights into diagnosis and therapy.Hematol/Oncol. Clinics North Am. 7, 109.Google Scholar
  27. 27.
    Alton, P.A. and Harris, A.L. (1993) The role of DNA topoisomerases II in drug resistance.Br. J. Haematol. 85, 241.PubMedCrossRefGoogle Scholar
  28. 28.
    Brito-Babapulle, V., Daly, P. and Catovsky, D. (1988) Possible association of disseminated intravascular coagulation (DIC) with the chromosomal region 17q12-21 and the gene for glycoprotein IIb-IIIa complex.Br. J. Haematol. 68, 142.PubMedCrossRefGoogle Scholar
  29. 29.
    Geurts van Kessel, A., de Leeuw, H., Dekker, E.J., Rijks, L., Spurr, N., Ledbetter, D., Kootwijk, E. and Vaessen, M.J. (1991) Localization of the cellular retinoic acid binding protein (CRABP) gene relative to the acute promyelocytic leukemia-associated breakpoint on human chromosome 15.Hum. Genet. 87, 201.PubMedCrossRefGoogle Scholar
  30. 30.
    Tallman, M., Gallagher, R.E. and Wiernik, P.H. (1995) Acute promyelocytic leukemia. In: P.H. Wiernik, G.P. Canellos, R.A. Kyle and J.P. Dutcher (eds)Neoplastic Diseases of the Blood, 3rd edn. New York: Churchill Livingston (in press).Google Scholar
  31. 31.
    Le Beau, M.M. (1993) Detecting genetic changes in human tumor cells: Have scientists ‘Gone Fishing’?Blood 81, 1979.PubMedGoogle Scholar
  32. 32.
    Bentz, M., Dohner, H., Cabot, G. and Lichter, P. (1994) Fluorescence in situ hybridization in leukemias: ‘The FISH are spawning!’Leukemia 8, 1447.PubMedGoogle Scholar
  33. 33.
    Oste, C. (1988) Polymerase chain reaction.BioTechniques 6, 162.PubMedGoogle Scholar
  34. 34.
    Kwok, S. and Higuchi, R. (1989) Avoiding false positives with PCR.Nature 339, 237.PubMedCrossRefGoogle Scholar
  35. 35.
    Cone, R.W. and Fairfax, M.R. (1993) Protocol for ultraviolet irradiation of surfaces to reduce PCR contamination.PCR Methods and Applications.3, S15. Cold Spring Harbor Laboratory ISSN.Google Scholar
  36. 36.
    Lestingi, T.M. and Hooberman, A.L. (1993) Philadelphia chromosome-positive acute lymphoblastic leukemia.Hematol/Oncol Clinics North Am. 7, 161.Google Scholar
  37. 37.
    Prokocimer, M. and Rotter, V. (1994) Structure and function of p53 in normal cells and their aberrations in cancer cells: projection on the hematologic cell lineages.Blood 84, 2391.PubMedGoogle Scholar
  38. 38.
    Imamura, J., Miyoshi, I. and Koeffler, H.P. (1994) p53 in hematologic malignancies.Blood 84, 2412.PubMedGoogle Scholar
  39. 39.
    Cohen, J.S. and Hogan, M.E. (1994) The new genetic medicines.Scient. Am. 271, 76.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1995

Authors and Affiliations

  • Elisabeth Paietta
    • 1
  1. 1.Department of OncologyMontefiore Medical and Albert Einstein Cancer CenterBronxUSA

Personalised recommendations