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Diminished A-LAK cytotoxicity and proliferation accompany disease
progression in chronic myelogenous leukemia
C Verfaillie, N Kay, W Miller and P McGlave
Department of Medicine, University of Minnesota Medical School, Minneapolis
55455.
We have compared the proliferative and cytotoxic capacities of a highly
purified population of recombinant interleukin-2 (rIL-2)-activated
peripheral blood mononuclear cells (PBMNC), termed adherent lymphokine-
activated killer cells (A-LAK), in 15 chronic phase (CP) and 10 advanced
disease (AD) Ph-positive chronic myelogenous leukemia (CML) patients. The
selective enrichment of CML A-LAK cells depended on their propensity to
adhere to plastic and to proliferate when cultured in the presence of rIL-2
for 14 days. In both CP and AD patients, 14-day culture resulted in growth
of a uniform population of large granular lymphocytes. While less than 10%
of the A-LAK cells were CD56-/CD3+ (mature T lymphocytes), 82% +/- 12% of
A-LAK cells from early CP patients (diagnosed less than 1 year from study),
84% +/- 3% of A-LAK cells from late CP patients (studied greater than 1
year after diagnosis), and 87% +/- 3% of A-LAK cells from AD patients were
CD56+/CD3- (activated natural killer [NK] cells). No bcr gene rearrangement
could be found in A-LAK cells from 13 CP and six AD CML patients studied.
A-LAK cells from seven early CP CML patients displayed similar cytotoxicity
against K562 (80% +/- 7% lysis at effector:target ratio of 20:1) and
against Raji (80% +/- 12% lysis) compared with A-LAK from 17 normal
individuals (72% +/- 3% K562 lysis, P = .21; 74% +/- 5% Raji lysis, P =
.39). However, the cytotoxicity of A-LAK cells from eight late CP patients
(59% +/- 5% K562 lysis, P = .02; 52% +/- 8% Raji lysis, P = .02) and that
of 10 AD patients studied at any point after diagnosis (31% +/- 3% K562
lysis, P less than .001; 25% +/- 6% Raji lysis, P less than .001) was
significantly lower than that of seven early CP CML patients and 17
normals. The proliferative potential of A-LAK cells from seven early CP CML
patients (291 +/- 191- fold) was significantly greater than that of A-LAK
cells from 17 normal individuals (23 +/- 3-fold, P = .03), eight late CP
patients (46 +/- 17- fold, P = .02), and 10 AD patients (5.4 +/- 1.9-fold,
P = .01). In contrast to CML A-LAK, K562 cytotoxicity of unstimulated
mature peripheral blood NK cells was significantly lower in early CP CML
patients than in normals and remained low at all stages of
disease.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 76,
Issue 2,
pp. 401-408,
07/15/1990
Copyright © 1990 by The American Society of Hematology
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