Effects of Growth Factors In Vitro on Acute Lymphoblastic Leukemia Cells

  • G. J. L. Kaspers
  • R. Pieters
  • C. H. Van Zantwijk
  • G. H. Broekema
  • K. Hählen
  • A. J. P. Veerman
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 37)


Growth factors may enhance the cytotoxicity of anticancer agents. Little is known about this effect of growth factors on acute lymphoblastic leukemia (ALL) cells. We studied the effects of interleukin-3 (IL-3), interleukin-7 (IL-7) and B-cell growth factor (BCGF) on cell survival and drug resistance in ALL samples, using the MTT assay.

Compared to drug-free culture without growth factors, the cell survival was significantly increased by IL- 3, IL-7 and BCGF. Compared to growth factor-free drug incubations, the cytotoxicity of thioguanine was significantly enhanced by IL- 3 and IL-7, and the cytotoxicity of cytarabine was significantly enhanced by IL-7. In contrast, the cytotoxicity of prednisolone was decreased by the growth factors in most ALL samples, and overall not significantly modulated.

We conclude that the MTT assay can be used to study the effects of growth factors on cell survival and drug resistance of ALL cells. This type of information may be useful for the design of clinical trials with growth factors in ALL.


Acute Lymphoblastic Leukemia Stimulation Index Acute Lymphoblastic Leukemia Cell Blast Cell Proliferation Stimulation Index Median 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Eder M, Ottmann OG, Hansen-Hagge TE, Bartram CR, Gillis S, Hoelzer D, Ganser A. Effects of human IL-7 on blast cell proliferation in acute lymphoblastic leukemia. Leukemia 1990, 4: 533–540PubMedGoogle Scholar
  2. 2.
    Estrov Z, Estey EH, Andreeff M, Talpaz M, Kurzrock R, Reading CL, Deisseroth AB, Gutterman JU. Comparison of in vivo and in vitro effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute myeoid leukemia. Exp Hematol 1992, 20: 558–564PubMedGoogle Scholar
  3. 3.
    Findley Jr HW, Zhou M, Davis R, Abdul-Rahim Y, Hnath R, Ragab AH. Effects of low molecular weight B-cell growth factor on proliferation of leukemic cells from children with B-cell precursor-acute lymphoblastic leukemia. Blood 1990, 75: 951–957PubMedGoogle Scholar
  4. 4.
    Kaspers GJL, Pieters R, Van Zantwijk CH, De Laat PAJM, De Waal FC, Van Wering ER, Veerman AJP. In vitro drug sensitivity of normal peripheral blood lymphocytes and childhood leukaemic cells from bone marrow and peripheral blood. Br J Cancer 1991, 64: 469–474PubMedCrossRefGoogle Scholar
  5. 5.
    Koistinen P, Wang C, Curtis JE, McCulloch EA. Granulocyte-macrophage colony-stimulatingfactor and interleukin-3 protect leukemic blast cells from ara-C toxicity. Leukemia 1991, 5: 789–795Google Scholar
  6. 6.
    Migliorati G, Nicoletti I, Pagliacci MC, D’Adamio L, Riccardi C. Interleukin-4 protects double-negative and CD4 single-positive thymocytes from dexamethasone-induced apoptosis. Blood 1993, 81: 1352–1358PubMedGoogle Scholar
  7. 7.
    Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 1983, 65: 55–63PubMedCrossRefGoogle Scholar
  8. 8.
    O’Connor R, Cesano A, Lange B, Finan J, Nowell PC, Clark SC, Raimondi SC, Rovera G, Santoli D. Growth factor requirements of childhood acute T-lymphoblastic leukemia: Correlation between presence of chromosomal abnormalities and ability to grow permanently in vitro. Blood 1991, 77: 1534–1545PubMedGoogle Scholar
  9. 9.
    Pieters R, Huismans DR, Leyva A, Veerman AJP. Adaptation of the rapid automated tetrazolium dye based MTT assay for chemosensitivity testing in childhood leukemia. Cancer Lett 1988, 41: 323–332PubMedCrossRefGoogle Scholar
  10. 10.
    Pieters R, Loonen AH, Huismans DR, Broekema GJ, Dirven MWJ, Heyenbrok MW, Hählen K, Veerman AJP. In vitro sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions. Blood 1990, 76: 2327–2336PubMedGoogle Scholar
  11. 11.
    Skjønsberg C, Erikstein BK, Smeland EB, Lie SO, Funderud S, Beiske K, Blomhoff HK. Interleukin-7 differentiates a subgroup of acute lymphoblastic leukemias. Blood 1991, 77: 2445–2550PubMedGoogle Scholar
  12. 12.
    Touw I, Pouwels K, Van Agthoven T, Van Gurp R, Budel L, Hoogerbrugge H, Delwel R, Goodwin R, Namen A, Löwenberg B. Interleukin-7 is a growth factor of precursor B and T acute lymphoblastic leukemia. Blood 1990, 75: 2097–2101PubMedGoogle Scholar
  13. 13.
    Uckun FM, Gesner TG, Song CW, Myers DE, Mufosn A. Leukemic B-cell precursors express functional receptors for human interleukin-3. Blood 1989, 73: 533–542PubMedGoogle Scholar
  14. 14.
    Veerman AJP, Pieters R. Drug sensitivity assays in leukaemia and lymphoma. Br J Haematol 1990, 74: 381–384PubMedCrossRefGoogle Scholar
  15. 15.
    Wörmann B, Mehta SR, Maizel AL, LeBien TW. Low molecular weight B cell growth factor induces proliferation of human B cell precursor acute lymphoblastic leukemias. Blood 1987, 70:132–138PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • G. J. L. Kaspers
    • 1
  • R. Pieters
    • 1
  • C. H. Van Zantwijk
    • 1
  • G. H. Broekema
    • 1
  • K. Hählen
    • 2
  • A. J. P. Veerman
    • 1
  1. 1.Department of PediatricsFree University HospitalAmsterdamThe Netherlands
  2. 2.Subdivision Hemato-/OncologySophia Children’s HospitalRotterdamThe Netherlands

Personalised recommendations