Cell proliferation and death: Forgotten features of chronic lymphocytic leukemia B cells
Cell proliferation and death: Forgotten features of chronic lymphocytic leukemia B cells
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DOI：
10.1016/j.beha.2007.03.007
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发表时间：
2007-09-01
影响因子：
2.1
通讯作者：
Chiorazzi, Nicholas
中科院分区：
文献类型：
--
作者：
Chiorazzi, Nicholas
慢性淋巴细胞性白血病(CLL)是由于出生率和死亡率之间的不平衡而导致异常B细胞的积累，使前者超过后者。这种失衡可能是出生人数增加、死亡人数减少或两者兼而有之的结果。长期以来，慢性淋巴细胞性白血病一直被认为是一种疾病，在这种疾病中，由于遗传缺陷，白血病克隆的出生最少，导致细胞积累。这一观点是在实验选择有限、体内和体外观察不太精确的情况下提出的--例如在光镜下，CLL细胞表现为静止的淋巴细胞，对有丝分裂原(主要是T细胞有丝分裂原)的反应很差--当时T和B细胞的区别还没有得到很好的认识。然而，最近使用更复杂的测量方法的研究表明，CLL生物学的初始特征需要重新评估。使用一种安全的、非放射性的体内标记方法，可以确定CLL细胞的出生率，我们直接证明了在所有研究的患者中，每天都有一小部分克隆(类似于0.1-1.75%)，即类似于I×109和I X 1012细胞出生。根据这个值，我们计算了单个患者的白血病细胞每天的死亡率在0到1×10 1 2之间。因此，出生和死亡之间的动态相互作用，这是其他白血病和淋巴瘤的特征，也适用于CLL。因此，CLL是一种增殖和蓄积并存的疾病，在这种疾病中，淋巴细胞计数稳定的患者存在动态平衡，或者淋巴细胞计数上升的患者存在失衡。
Chronic lymphocytic leukemia (CLL) results from an accumulation of abnormal B cells due to an imbalance between birth and death rates such that the former exceeds the latter. This imbalance can occur as a result of increased birth, decreased death, or a combination of the two. CLL has long been considered a disease in which cell accumulation results from decreased death, due to a genetic defect, with minimal birth of the leukemic clone. This view was promulgated when experimental options were limited and observations in vivo and in vitro were less precise-e.g. CLL cells appeared as resting lymphocytes by light microscopy and responded poorly to mitogens (primarily T-cell mitogens)-at a time when T- and B-cell discrimination was not well appreciated. However, recent studies using more sophisticated measures suggest that the initial characterization of CLL biology needs re-evaluation. Using a safe, non-radioactive in-vivo labeling method that permits the determination of CLL-cell birth rates, we have directly documented that a small fraction of the clone (similar to 0.1-1.75%.), i.e., between similar to I x 109 and I X 1012 cells are born each day in all patients studied. With this value, we calculated death rates of between 0 and I X 10 1 2 per day of leukemic cells from individual patients. Thus the dynamic interplay between birth and death that characterizes other leukemias and lymphomas applies to CLL. Therefore, CLL is a disease of both proliferation and accumulation in which a homeostatic balance exists in patients with stable lymphocyte counts or an imbalance exists in patients with rising lymphocyte counts.