Low BCL-2 expression in acute leukemia with t(8;21) chromosomal abnormality

被引:18
作者
Shikami, M
Miwa, H
Nishii, K
Takahashi, T
Sekine, T
Mahmud, N
Nishikawa, M
Shiku, H
Kamada, N
Kita, K
机构
[1] Mie Univ, Sch Med, Dept Internal Med 2, Tsu, Mie 5148507, Japan
[2] Hiroshima Univ, Nucl Med & Biol Res Inst, Dept Hematol, Hiroshima, Japan
关键词
t(8; 21)AML; BCL-2; cell cycle;
D O I
10.1038/sj.leu.2401343
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In de novo 1(8;21) AML which shows terminal neutrophilic differentiation, the BCL-2 expression was found to he significantly lower than that in types of other AML regardless of the phenotypic differentiation status. An inverse correlation between BCL-2 expression and the S/G(2)/M population cells was observed in AML. The S/G(2)/M population in t(8;21)AML was larger than in the other types of AML. In t(8;21)AML, spontaneous apoptosis after a 12-h liquid culture was prominent, and the autonomous DNA synthesis after a 72-h liquid culture was low. G-CSF and IL-5 promoted the colony formation of t(8;21)AML cells. The data suggest that, in vivo, the tow BCL-2 in t(8;21)AML induced entry of cells from the G(0)/G(1) phase to S phase, but the cells easily die by apoptosis, in vitro. The low BCL-2 expression and the supportive effects of G-CSF and IL-5 in t(8;21)AML is thought to be a key phenomenon which might he related to the formation of the in vivo brood picture, such as prominent neutrophilic differentiation and eosinophilia. Cellular extracts from t(8;21)AML cell line Kasumi-1 bound to both the AML1 and CRE binding sites in the bcl-2 promoter, but none of the cellular extracts from de novo t(8;21)AML bound to either of these sites. The DNA binding activity of transactivators in de novo t(8;21)AML is different from that in Kasumi-1 cells probably due to the phosphorylation status.
引用
收藏
页码:358 / 368
页数:11
相关论文
共 50 条
[21]  
KITA K, 1992, BLOOD, V80, P470
[22]  
KITA K, 1993, BLOOD, V81, P2399
[23]   EXPRESSION CLONING OF THE HUMAN IL-3 RECEPTOR CDNA REVEALS A SHARED BETA-SUBUNIT FOR THE HUMAN IL-3 AND GM-CSF RECEPTORS [J].
KITAMURA, T ;
SATO, N ;
ARAI, K ;
MIYAJIMA, A .
CELL, 1991, 66 (06) :1165-1174
[24]   The AML1/ETO fusion protein activates transcription of BCL-2 [J].
Klampfer, L ;
Zhang, J ;
Zelenetz, AO ;
Uchida, H ;
Nimer, SD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :14059-14064
[25]   AUTONOMOUS PROLIFERATION OF LEUKEMIC-CELLS INVITRO AS A DETERMINANT OF PROGNOSIS IN ADULT ACUTE MYELOID-LEUKEMIA [J].
LOWENBERG, B ;
VANPUTTEN, WLJ ;
TOUW, IP ;
DELWEL, R ;
SANTINI, V .
NEW ENGLAND JOURNAL OF MEDICINE, 1993, 328 (09) :614-619
[26]  
MARVEL J, 1994, ONCOGENE, V9, P1117
[27]  
MASUYA M, 1993, BLOOD, V81, P3388
[28]   Regulation of cell division cycle progression by bcl-2 expression: A potential mechanism for inhibition of programmed cell death [J].
Mazel, S ;
Burtrum, D ;
Petrie, HT .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (05) :2219-2226
[29]   T(8-21) BREAKPOINTS ON CHROMOSOME-21 IN ACUTE MYELOID-LEUKEMIA ARE CLUSTERED WITHIN A LIMITED REGION OF A SINGLE GENE, AML1 [J].
MIYOSHI, H ;
SHIMIZU, K ;
KOZU, T ;
MASEKI, N ;
KANEKO, Y ;
OHKI, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (23) :10431-10434
[30]   THE T(8-21) TRANSLOCATION IN ACUTE MYELOID-LEUKEMIA RESULTS IN PRODUCTION OF AN AML1-MTG8 FUSION TRANSCRIPT [J].
MIYOSHI, H ;
KOZU, T ;
SHIMIZU, K ;
ENOMOTO, K ;
MASEKI, N ;
KANEKO, Y ;
KAMADA, N ;
OHKI, M .
EMBO JOURNAL, 1993, 12 (07) :2715-2721