Telomere shortening in patients with plasma cell disorders
Telomere shortening in patients with plasma cell disorders
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DOI：
10.1034/j.1600-0609.2003.00157.x
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发表时间：
2003-11-01
影响因子：
3.1
通讯作者：
Slavutsky, I
中科院分区：
文献类型：
--
作者：
Cottliar, A;Pedrazzini, E;Slavutsky, I
目的：端粒对维持染色体的完整性至关重要，端粒的缩短与染色体的不稳定性有关。为研究多发性骨髓瘤（MM）和意义不明的单克隆丙种球蛋白病（MGUS）患者骨髓细胞端粒长度（TL），对31例MM患者（确诊时12例，复发时11例，缓解时8例）和2例MGUS患者进行了研究。评价了基于末端限制性片段（TRF）测定的TL。进行细胞遗传学和分子细胞遗传学分析。结果：所有MM患者的TRF分析显示平均TRF峰值（5.20 ± 0.35 kb）短于对照组（8.5 ± 0.5 kb）（P < 0.001）。此外，在D和R时TRF显示端粒明显缩短（P < 0.001），在RE时TL恢复。骨髓浆细胞浸润率（BM plasma cell infiltration，BMPCI）与TRFs呈显著正相关（rK = -0.540; P = 0.002），异常核型（AK）患者的TRFs明显短于正常核型患者（P < 0.05）。MGUS患者的TRF与对照组无差异。TA分析显示MM患者的TL百分比（19.46 ± 1.98%）高于MGUS（6.12 ± 1.87%）和正常BM细胞（2.00 ± 0.93%）（P < 0.001）。此外，我们的研究结果支持端粒缩短通常导致TA和染色体不稳定性频率增加的观点。
Objectives: Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).Methods: Thirty-one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight at remission (RE) and two cases with MGUS were studied. TL based on terminal restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular cytogenetic analyses were performed. Telomeric associations (TAs) on BM metaphases were also studied.Results: TRF analysis in total MM patients showed a mean TRF peak value (5.20 +/- 0.35 kb) shorter than those observed in controls (8.5 +/- 0.5 kb) (P < 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P < 0.001), with TL restored at RE. A strong correlation with the percentage of BM plasma cell infiltration (BMPCI) (rK = -0.540; P = 0.002) was found. Patients with abnormal karyotypes (AK) had significantly shorter TRFs than that observed in MM patients with normal karyotypes (P < 0.05). TRFs in MGUS patients did not differ with respect to controls. TA analysis showed an increased percentage in MM (19.46 +/- 1.98%) with respect to MGUS (6.12 +/- 1.87%) and normal BM cells (2.00 +/- 0.93%) (P < 0.001).Conclusions: MM patients showed a significant reduction in TL (>60% of BMPCI and AK), suggesting a probable association with clinical evolution. Moreover, our findings support the idea that telomere shortening usually leads to increased frequencies of TAs and chromosome instability.