In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells
In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells
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DOI：
10.1172/jci23409
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发表时间：
2005-03-01
影响因子：
15.9
通讯作者：
Chiorazzi, N
中科院分区：
文献类型：
--
作者：
Messmer, BT;Messmer, D;Chiorazzi, N
由于其相对缓慢的临床进展，B细胞慢性淋巴细胞白血病（B-CLL）被经典地描述为积聚而不是增殖的疾病。然而，各种形式的克隆进化的证据表明，B-CLL克隆可能比以前假设的更具活力。我们使用了非放射性的，稳定的同位素标记方法来测量B-CLL细胞在体内的动力学。19例患者每天饮用一等份的氘化水（（H2O）-H-2），持续84天，并通过气相色谱/质谱法测量新分裂的B-CLL细胞DNA的脱氧核糖部分中的H-2掺入，在标记期间和之后。根据动力学曲线计算出生率。死亡率被定义为计算的出生率和生长率之间的差异。这些分析表明，每个患者的白血病细胞具有可定义的并且通常是实质性的出生率，从每天整个克隆的0.1%到大于1.0%不等。那些出生率高于每天0.35%的患者比出生率较低的患者更有可能表现出活动性或进展性疾病。因此，B-CLL不是一种简单地由长寿淋巴细胞积累引起的静态疾病。相反，它是一个动态的过程，也包括细胞增殖和死亡，通常在可感知的水平。这种更替的程度以前没有得到重视。出生率与疾病活动和进展之间似乎存在相关性，这可能有助于在临床恶化之前识别有疾病恶化风险的患者。
Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water ((H2O)-H-2) daily for 84 days, and H-2 incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1% to greater than 1.0% of the entire clone per day. Those patients with birth rates greater than 0.35% per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.