Assessment of therapeutic potential of interleukin 2 for myelodysplastic syndromes.
The therapeutic potential of interleukin 2 (IL-2) for myelodsplastic syndromes (MDS) was evaluated in vitro. IL-2-induced lymphokine-activated killer (LAK) cells were prepared from 38 MDS patients and 20 normal subjects. The cytotoxicity of LAK cells against K562 and Raji cell lines and MDS blasts was significantly reduced in high-risk MDS (refractory anaemia with excess blasts (RAEB), RAEB in transformation, and leukaemic transformation of MDS), but was relatively well-preserved in low-risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts). Examination of the immunophenotypes of freshly-isolated lymphocytes showed that the percentage of CD4+ cells in low-risk MDS and the percentage of CD3+, CD4+ and CD8+ cell populations in high-risk MDS was significantly reduced compared with these populations in normal subjects. After cultivation with IL-2, these three cell populations were still reduced in the corresponding MDS groups and the percentage of CD3-CD56+ cells were significantly reduced in high-risk MDS. There was a positive correlation between the percentage of K562 cells lysed by MDS LAK cells and the percentage of CD3-CD56+ lymphocytes in MDS LAK cells. These aberrant lymphocyte subpopulations appeared to explain, at least in part, the reduced LAK cell cytotoxicity in MDS. These results present a possibility that IL-2 and LAK therapies are ineffective for most high-risk MDS patients, whereas they have potential value for low-risk MDS patients whose lymphocyte cytotoxicity is usually preserved.
Ogata
K
K
Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Yokose
N
N
Ito
T
T
An
E
E
Tamura
H
H
Dan
K
K
Hamaguchi
H
H
Sakamaki
H
H
Onozawa
Y
Y
Nomura
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology* / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000628:therapy; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D007376:Interleukin-2