APOPTOSIS IN BONE-MARROW BIOPSY SAMPLES INVOLVING STROMAL AND HEMATOPOIETIC-CELLS IN 50 PATIENTS WITH MYELODYSPLASTIC SYNDROMES

APOPTOSIS IN BONE-MARROW BIOPSY SAMPLES INVOLVING STROMAL AND HEMATOPOIETIC-CELLS IN 50 PATIENTS WITH MYELODYSPLASTIC SYNDROMES
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DOI:
10.1182/blood.v86.1.268.bloodjournal861268
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发表时间:
1995-07-01
期刊:
影响因子:
20.3
通讯作者:
PREISLER, H
PREISLER, H
中科院分区:
医学1区
文献类型:
--
作者:
RAZA, A;GEZER, S;PREISLER, H

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对50例骨髓增生异常综合征(MDS)患者进行原位碘脱氧尿嘧啶和/或溴脱氧尿嘧啶输注后的细胞周期动力学测量,骨髓(BM)活检样本的中位标记指数为28.6%。不幸的是,原位末端标记(ISEL)技术显示,50例患者中的26例显示,所有三个谱系的造血细胞在其活检样本中发生了大于或等于75%的程序性细胞死亡(PCD)。10例患者ISEL(+)细胞为1/3,8例为2/3。基质细胞常为ISEL(+), s期细胞常同时为ISEL(+)。核小体DNA片段在琼脂糖凝胶中作为阶梯存在于4例高ISEL患者的BM抽吸液中,而在活检样本中没有ISEL染色的2例患者中则不存在,但只有在完全培养液中体外培养4小时后提取DNA时才存在。因此,阶梯数据证实了ISEL的发现,即MDS中的大多数造血细胞处于PCD的早期阶段。我们得出结论,广泛的髓内细胞死亡可能解释了MDS患者尽管有高细胞骨髓但全血细胞减少的悖论。研究在某些MDS子集中防止PCD的方法将是令人感兴趣的。(C) 1995年由美国血液病学会出版。
Cell-cycle kinetics were measured in situ after infusions of iododeoxyuridine and/or bromodeoxyuridine in 50 patients with myelodysplastic syndromes (MDS) and the median labeling index in bone marrow (BM) biopsy samples was 28.6%. Unfortunately, 26 of 50 patients showed that greater than or equal to 75% of hematopoietic cells of all three lineages were undergoing programmed cell death (PCD) in their biopsy samples as shown by the in situ end labeling (ISEL) technique. Ten patients had 1/3 and eight had 2/3 ISEL(+) cells. Stromal cells were frequently ISEL(+) and often S-phase cells were also found to be simultaneously ISEL(+). Nucleosomal DNA fragments as a ladder in agarose gel were present in BM aspirates of four patients who showed high ISEL and were absent in two who had no ISEL staining in biopsy samples, but only when DNA was extracted after a 4-hour in vitro incubation in complete medium. Therefore, laddering data confirmed the ISEL findings that the majority of hematopoietic cells in MDS are in early stages of PCD. We conclude that extensive intramedullary cell death may explain the paradox of pancytopenia despite hypercellular marrows in MDS patients. Investigating approaches that protect against PCD in some MDS subsets would be of interest. (C) 1995 by The American Society of Hematology.