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Interleukin-4 induces programmed cell death (apoptosis) in cases of
high-risk acute lymphoblastic leukemia
A Manabe, E Coustan-Smith, M Kumagai, FG Behm, SC Raimondi, CH Pui and D Campana
Department of Hematology-Oncology, St Jude Children's Research Hospital,
Memphis, TN 38101.
We investigated the effects of interleukin-4 (IL-4) on the survival of
leukemic and normal B-cell progenitors cultured on bone marrow stroma. IL-4
(at 100 U/mL) was cytotoxic in 16 of 21 cases of B-lineage acute
lymphoblastic leukemia, causing reductions in CD19+ cell numbers that
ranged from 50% to greater than 99% (median 83.5%) of those in parallel
cultures not exposed to the cytokine. All nine cases with the
t(9;22)(q34;q11) or the t(4;11)(q21;q23), chromosomal features that are
often associated with multidrug resistance and a fatal outcome, were
susceptible to IL-4 toxicity. IL-4 cytotoxicity resulted from induction of
programmed cell death (apoptosis); there was no evidence of cell killing
mediated by T, natural killer, or stromal cells. IL-4 cytotoxicity extended
to a proportion of normal B-cell progenitors. After 7 days of culture with
IL-4 at 100 U/mL, fewer CD19+, CD34+ normal lymphoblasts (the most immature
subset) survived: in five experiments the mean (+/- SEM) reduction in cell
recoveries caused by IL-4 was 60.0% +/- 6.0%. By contrast, reductions in
recovery of more differentiated bone marrow B cells (CD19+, CD34-, surface
Ig+) were low (6.6% +/- 2.2%; P < .001 by t-test). Our findings indicate
that IL-4 is cytotoxic for human B-cell precursors and support clinical
testing of IL-4 in cases of high-risk lymphoblastic leukemia resistant to
conventional therapy.
Volume 83,
Issue 7,
pp. 1731-1737,
04/01/1994
Copyright © 1994 by The American Society of Hematology
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