Diminished A-LAK cytotoxicity and proliferation accompany disease progression in chronic myelogenous leukemia.
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)
Verfaillie
C
C
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
Kay
N
N
Miller
W
W
McGlave
P
P
D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D019002:CD56 Antigen; D002448:Cell Adhesion; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000473:pathology; D010677:Philadelphia Chromosome; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019002:CD56 Antigen; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins