scholarly journals Autocrine growth of interleukin 2-producing leukemic cells in a patient with adult T cell leukemia

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 779-782 ◽  
Author(s):  
N Arima ◽  
Y Daitoku ◽  
S Ohgaki ◽  
J Fukumori ◽  
H Tanaka ◽  
...  

Abstract Leukemic cells in the peripheral blood of a patient with adult T cell leukemia (ATL), which expressed the Tac antigen/interleukin 2 (IL2) receptor, were investigated in vitro for autocrine growth by IL 2. The cells showed spontaneous proliferation in mitogen-free medium. The spontaneous proliferation of the cells was inhibited by monoclonal anti- IL 2 or anti-Tac antibody. These cells were found to produce messenger RNA for IL 2 and secrete IL 2 during short-term culture in the same medium. Recombinant IL 2 and IL 2 secreted by the cells enhanced the proliferation of the cells in a dose-dependent manner when added to the initial culture. These findings demonstrate that an autocrine mechanism by IL 2 is involved in the proliferation of ATL cells during short-term culture.

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 779-782 ◽  
Author(s):  
N Arima ◽  
Y Daitoku ◽  
S Ohgaki ◽  
J Fukumori ◽  
H Tanaka ◽  
...  

Leukemic cells in the peripheral blood of a patient with adult T cell leukemia (ATL), which expressed the Tac antigen/interleukin 2 (IL2) receptor, were investigated in vitro for autocrine growth by IL 2. The cells showed spontaneous proliferation in mitogen-free medium. The spontaneous proliferation of the cells was inhibited by monoclonal anti- IL 2 or anti-Tac antibody. These cells were found to produce messenger RNA for IL 2 and secrete IL 2 during short-term culture in the same medium. Recombinant IL 2 and IL 2 secreted by the cells enhanced the proliferation of the cells in a dose-dependent manner when added to the initial culture. These findings demonstrate that an autocrine mechanism by IL 2 is involved in the proliferation of ATL cells during short-term culture.


Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1407-1411 ◽  
Author(s):  
M Maeda ◽  
N Arima ◽  
Y Daitoku ◽  
M Kashihara ◽  
H Okamoto ◽  
...  

Abstract Interleukin 2 (IL-2) receptor/Tac antigen is abnormally expressed on cells of patients with adult T cell leukemia (ATL) caused by infection with human T lymphotropic virus type I (HTLV-I). Twenty-five patients with ATL were examined to determine whether their leukemic cells continued to show IL-2-dependent proliferation. In 21 patients, the in vitro proliferation of HTLV-I-infected nonleukemic T cell clones was found to be dependent on IL-2. However, clonality analysis based on T cell receptor gene rearrangement profiles and the site of HTLV-I provirus integration revealed IL-2-dependent growth in leukemic cells in four patients with ATL. These results provide evidence for the IL-2- dependent proliferation of leukemic cells in some ATL patients.


1996 ◽  
Vol 20 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Kakushi Matsushita ◽  
Naomichi Arima ◽  
Toshinobu Fujiyoshi ◽  
Yasuhisa Daitoku ◽  
Shiroh Hidaka ◽  
...  

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1182-1186 ◽  
Author(s):  
T Uchiyama ◽  
M Kamio ◽  
T Kodaka ◽  
S Tamori ◽  
S Fukuhara ◽  
...  

Abstract The proliferative response of fresh peripheral blood leukemic cells from eight adult T cell leukemia (ATL) patients to interleukin-4 (IL-4) was studied to determine the possibility that the IL-4-mediated T-cell growth pathway is involved in the cell growth of leukemic cells in ATL. Resting lymphocytes from ten normal individuals did not proliferate in response to IL-4. Leukemic cells from two ATL patients did not respond to interleukin-2 (IL-2) or IL-4. Leukemic cells from two patients did respond to IL-2, but not to IL-4. In contrast, a strong proliferative response was observed in the IL-4 culture, but not in the IL-2 culture in the remaining four patients. Chromosome analysis of mitotic cells, performed in one of four patients, confirmed that the cells dividing in response to IL-4 were leukemic cells, but not activated normal lymphocytes. These results indicate the activation of IL-4/IL-4 receptor system in leukemic cells from some ATL patients and suggest the possible involvement of the system in the proliferation of leukemic cells and the leukemogenesis in ATL.


1990 ◽  
Vol 81 (9) ◽  
pp. 902-908 ◽  
Author(s):  
Taiichi Kodaka ◽  
Takashi Uchiyama ◽  
Takayuki Ishikawa ◽  
Masanori Kamio ◽  
Rie Onishi ◽  
...  

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1182-1186
Author(s):  
T Uchiyama ◽  
M Kamio ◽  
T Kodaka ◽  
S Tamori ◽  
S Fukuhara ◽  
...  

The proliferative response of fresh peripheral blood leukemic cells from eight adult T cell leukemia (ATL) patients to interleukin-4 (IL-4) was studied to determine the possibility that the IL-4-mediated T-cell growth pathway is involved in the cell growth of leukemic cells in ATL. Resting lymphocytes from ten normal individuals did not proliferate in response to IL-4. Leukemic cells from two ATL patients did not respond to interleukin-2 (IL-2) or IL-4. Leukemic cells from two patients did respond to IL-2, but not to IL-4. In contrast, a strong proliferative response was observed in the IL-4 culture, but not in the IL-2 culture in the remaining four patients. Chromosome analysis of mitotic cells, performed in one of four patients, confirmed that the cells dividing in response to IL-4 were leukemic cells, but not activated normal lymphocytes. These results indicate the activation of IL-4/IL-4 receptor system in leukemic cells from some ATL patients and suggest the possible involvement of the system in the proliferation of leukemic cells and the leukemogenesis in ATL.


Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1407-1411 ◽  
Author(s):  
M Maeda ◽  
N Arima ◽  
Y Daitoku ◽  
M Kashihara ◽  
H Okamoto ◽  
...  

Interleukin 2 (IL-2) receptor/Tac antigen is abnormally expressed on cells of patients with adult T cell leukemia (ATL) caused by infection with human T lymphotropic virus type I (HTLV-I). Twenty-five patients with ATL were examined to determine whether their leukemic cells continued to show IL-2-dependent proliferation. In 21 patients, the in vitro proliferation of HTLV-I-infected nonleukemic T cell clones was found to be dependent on IL-2. However, clonality analysis based on T cell receptor gene rearrangement profiles and the site of HTLV-I provirus integration revealed IL-2-dependent growth in leukemic cells in four patients with ATL. These results provide evidence for the IL-2- dependent proliferation of leukemic cells in some ATL patients.


Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2900-2904 ◽  
Author(s):  
N Arima ◽  
S Hidaka ◽  
H Fujiwara ◽  
K Matsushita ◽  
H Ohtsubo ◽  
...  

We examined autonomous and interleukin-2 (IL-2)-responsive growth activities of leukemic cells derived from peripheral blood, as well as several clinical manifestations, including serum lactate dehydrogenase (LDH) level, of 35 patients with adult T-cell leukemia (ATL) to determine whether these properties were related to prognosis. Growth activities were measured by [3H]-thymidine incorporation of the cells after 24 hours' culture with or without exogenous IL-2. Both autonomous and IL-2-responsive growth activities were higher in the patients than in healthy controls and were significantly correlated with each other (P < .0001, r = .956). Both higher growth activities were significantly associated with shorter survival times (P = .0042, r = .472 and P = .0117, r = .421, respectively). An increased serum LDH value was also significantly associated with shorter survival times (P = .0011, r = .530), but corrected calcium level, sex, white blood cell count, or age were not. These results strongly suggest that both growth activities of primary tumor cells, in addition to the serum LDH value, are prognostic determinants in ATL. We propose a new prognostic classification combining LDH values and autonomous growth activity into three groups: (1) high growth activity and high LDH; (2) high growth activity and low LDH, or low growth activity and high LDH; and (3) low growth activity and low LDH, which showed a significant relationship to survival time (P = .0014; the median survival time for each group was 39, 94, and 340 days, respectively).


Sign in / Sign up

Export Citation Format

Share Document