Kawabata H, Anzai N, Ueda Y, Masutani H, Hirama T, Yoshida Y, Okuma M
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Leukemia. 1996 Jan;10(1):67-73.
The endogenous endonucleases capable of producing nucleosomal-size DNA fragmentation are considered candidates of the key enzyme of apoptosis. We examined these activities in the nuclear fraction of non-adherent marrow mononuclear cells (NonAd-MNCs) from patients with myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) using a nuclear autodigestion method. We detected Ca2+/Mg(2+)-dependent endonuclease activity in all samples examined. In contrast, Ca(2+)-independent activity with the ability to produce nucleosomal-size DNA fragmentation was found only in samples from a proportion of patients with MDS (12 of 26 consecutive cases) and all the patients with AML (n = 6), but not in the samples from control group patients (n = 10). This activity was correlated with the percentage of bone marrow (BM) blast cells to some extent. Although the levels of these endogenous endonuclease activities seem not to be correlated directly with the susceptibility of the cells to apoptosis, we postulate that the Ca(2+)-independent endonuclease activity may be associated with apoptosis and/or cell proliferation. Further follow-up study of these patients may be meaningful to clarify the prognostic significance of the Ca(2+)-independent endonuclease activity in patients with MDS.
能够产生核小体大小DNA片段的内源性核酸内切酶被认为是凋亡关键酶的候选者。我们采用核自消化法检测了骨髓增生异常综合征（MDS）和急性髓性白血病（AML）患者非贴壁骨髓单个核细胞（NonAd-MNCs）核组分中的这些活性。在所有检测样本中我们都检测到了Ca2+/Mg(2+)依赖性核酸内切酶活性。相反，仅在一部分MDS患者（连续26例中的12例）和所有AML患者（n = 6）的样本中发现了具有产生核小体大小DNA片段能力的Ca(2+)非依赖性活性，而对照组患者（n = 10）的样本中未发现。这种活性在一定程度上与骨髓（BM）原始细胞百分比相关。尽管这些内源性核酸内切酶活性水平似乎与细胞对凋亡的易感性没有直接关联，但我们推测Ca(2+)非依赖性核酸内切酶活性可能与凋亡和/或细胞增殖有关。对这些患者进行进一步的随访研究可能有助于阐明Ca(2+)非依赖性核酸内切酶活性在MDS患者中的预后意义。
