GU National Research Center for Hematology, Russian Academy of Medical Sciences.
Acta Naturae. 2009 Oct;1(3):108-20.
Cell regulation of Ph(+)cell proliferation and differentiation has been studied ex vivo in various chronic myeloid leukemia (CML) patients. The regulation is provided by alternation of effective stages of proliferation and maturation with inhibition of Ph(+) cell proliferation by accumulating neutrophils under apoptosis blockage. The alternation of stages consists of switching stage 1 (effective proliferation) to stage 2 (effective maturation) and proceeds according to the 1/2 -1/2/1 or 2/1-2/1/2/1 schemes. The kinetic plots of alternations pass through control points of crossing plots, where the parameters of proliferation and maturation are equal. The indices of P/D efficiency (ratio of proliferation and maturation rates) are 1.06±0.23 and don't depend on time, alternation order, or sources of Ph(+) cells - CML patients. During stages alternation, conversely, the parameters of Ph+ cell proliferation and maturation vary. The proliferation stages are characterized by increased proliferating cells content, a decreased number of neutrophils, and apoptosis induction. At the maturation stages, conversely, apoptosis is inhibited, the number of mature neutrophils increases, while immature Ph(+) cells decrease. High content neutrophils inhibit the proliferation of Ph(+) cells and impair their own maturation by inversion of maturation order, probably through a feedback mechanism. The regulation differences ex vivo reveal three types of Ph(+) cells from various individual CML patients, distinguished by the number and duration of alternating stages of proliferation and maturation. Ph(+) cells types 1 and 2 have one prolonged stage of effective proliferation or effective maturation with efficiency indices P/D(1) = 1-20 or P/D(2) ⇐ 1. At the same time period, the proliferation and differentiation of the Ph(+) cells type 3 proceeds with repeated alternations of stages with P/D(1) = 1-4 or P/D(2) ⇐ 1. Type 1 Ph(+) cells (~20%) were isolated from patients in advanced stages of CML, while Ph(+) cells types 2 and 3 (30 and 50% correspondingly) were isolated from CML chronic phase patients sensitive to chemotherapy.
Ph(+) 细胞的增殖和分化的细胞调控已在各种慢性髓性白血病 (CML) 患者的体外研究中进行。调控是通过在阻止细胞凋亡的情况下，积累中性粒细胞来抑制 Ph(+)细胞增殖，同时交替增殖和成熟的有效阶段来实现的。阶段的交替包括将阶段 1（有效增殖）切换到阶段 2（有效成熟），并根据 1/2-1/2/1 或 2/1-2/1/2/1 方案进行。交替的动力学曲线通过交叉点的控制点，其中增殖和成熟的参数相等。增殖和成熟效率的指数（增殖和成熟率的比值）为 1.06±0.23，且不依赖于时间、交替顺序或 Ph(+)细胞的来源 - CML 患者。相反，在阶段交替期间，Ph+细胞增殖和成熟的参数会发生变化。增殖阶段的特征是增殖细胞含量增加、中性粒细胞数量减少和诱导细胞凋亡。相反，在成熟阶段，细胞凋亡受到抑制，成熟中性粒细胞数量增加，而不成熟 Ph(+)细胞减少。高含量的中性粒细胞通过成熟顺序的反转来抑制 Ph(+)细胞的增殖并损害它们自身的成熟，可能通过反馈机制。体外的调控差异揭示了来自不同个体 CML 患者的三种类型的 Ph(+)细胞，它们的区别在于增殖和成熟阶段的数量和持续时间。Ph(+)细胞类型 1 和 2 有一个延长的有效增殖或有效成熟阶段，效率指数 P/D(1) = 1-20 或 P/D(2) ⇐ 1。在同一时间段内，Ph(+)细胞类型 3 的增殖和分化则通过重复交替的阶段进行，P/D(1) = 1-4 或 P/D(2) ⇐ 1。Ph(+)细胞类型 1（~20%）从 CML 晚期患者中分离出来，而 Ph(+)细胞类型 2 和 3（分别为 30%和 50%）从对化疗敏感的 CML 慢性期患者中分离出来。
