High levels of Ca(2+)-independent endonuclease activity capable of producing nucleosomal-size DNA fragmentation in non-adherent marrow mononuclear cells from patients with myelodysplastic syndromes and acute myelogenous leukemia.
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.
Kawabata
H
H
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Anzai
N
N
Ueda
Y
Y
Masutani
H
H
Hirama
T
T
Yoshida
Y
Y
Okuma
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001853:Bone Marrow / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009707:Nucleosomes / Q000378:metabolism*; D011379:Prognosis
D009707:Nucleosomes; D004247:DNA; D004720:Endonucleases; D002118:Calcium