Agis H, Jaeger E, Doninger B, Sillaber C, Marosi C, Drach J, Schwarzinger I, Valent P, Oehler L
Department of Internal Medicine I, Vienna Medical University, Vienna, Austria.
Eur J Clin Invest. 2006 Jun;36(6):402-8. doi: 10.1111/j.1365-2362.2006.01645.x.
Imatinib mesylate has considerable antineoplastic activity in patients with chronic myeloid leukaemia (CML) and some solid tumours. Although originally regarded as nontoxic for normal haematopoiesis, mild to moderate myelosuppression is a commonly observed side-effect of this treatment. Recently, this molecule has been shown to suppress normal haematopoietic progenitor cells in vitro. This is the first study that has investigated the effect of imatinib on haematopoietic progenitor cells in vivo.
We investigated the number of circulating haematopoietic progenitor cells in 79 patients with CML and five patients with solid tumours who were treated with imatinib for at least 3 months. Bone marrow progenitor cells were assessed in a subgroup of 18 patients with CML after 12 months of imatinib treatment. Results were compared with haematopoietic progenitor cell numbers of normal controls.
Circulating progenitors of all classes were significantly decreased in CML up to 24 months of imatinib therapy compared with healthy controls (median progenitor cells in CML after 12 months: CFU-GM 62, range 0-2543; BFU-E 216, range 0-3259; CFU-GEMM 0, range 0-139; versus controls: CFU-GM 208, range 50-936; BFU-E 690, range 120-1862; CFU-GEMM 20, range 4-77; P < 0.001). Similar reductions in the number of progenitor cells derived from bone marrow were found in a subgroup of 18 patients with CML. In patients with solid tumours the number of circulating progenitor cells was significantly lower under treatment with imatinib when compared with the controls. Withdrawal of imatinib in a patient with a malignant brain tumour resulted in a prompt normalization of circulating progenitors.
This study suggests that imatinib exerts myelosuppressive effects through inhibition of haematopoietic progenitor cells.
甲磺酸伊马替尼对慢性粒细胞白血病（CML）患者及部分实体瘤患者具有显著的抗肿瘤活性。尽管最初认为其对正常造血无毒性，但轻度至中度骨髓抑制是该治疗常见的副作用。最近，该分子已被证明在体外可抑制正常造血祖细胞。这是第一项研究伊马替尼对体内造血祖细胞影响的研究。
我们调查了79例CML患者和5例实体瘤患者循环造血祖细胞的数量，这些患者接受伊马替尼治疗至少3个月。在18例CML患者接受伊马替尼治疗12个月后，对其骨髓祖细胞进行评估。将结果与正常对照的造血祖细胞数量进行比较。
与健康对照相比，在伊马替尼治疗长达24个月的CML患者中，各类循环祖细胞均显著减少（伊马替尼治疗12个月后CML患者的祖细胞中位数：CFU-GM 62，范围0 - 2543；BFU-E 216，范围0 - 3259；CFU-GEMM 0，范围0 - 139；对照：CFU-GM 208，范围50 - 936；BFU-E 690，范围120 - 1862；CFU-GEMM 20，范围4 - 77；P < 0.001）。在18例CML患者的亚组中，发现来自骨髓的祖细胞数量有类似减少。与对照相比，实体瘤患者在接受伊马替尼治疗时循环祖细胞数量显著降低。一名恶性脑肿瘤患者停用伊马替尼后，循环祖细胞迅速恢复正常。
本研究表明伊马替尼通过抑制造血祖细胞发挥骨髓抑制作用。
