Tokunaga Y, Miyamoto T, Okamura T, Eto T, Gondo H, Kamimura T, Okamura S, Niho Y
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Br J Haematol. 1998 Sep;102(5):1232-40. doi: 10.1046/j.1365-2141.1998.00915.x.
We investigated the effect of thrombopoietin (TPO) on the growth of leukaemic blasts from 30 acute myelogenous leukaemia (AML) patients according to the surface expression of CD7 and CD34: 10 patients were CD7 positive (CD7+), nine were CD7 negative/CD34+ (CD7-/CD34+) and the remaining 11 were CD7-/CD34-. Significant growth response of leukaemic blasts to TPO was observed in 10/10 CD7+, 5/9 CD7-/CD34+ and 2/11 CD7-/CD34- AML cases using 3H-thymidine incorporation. Synergistic stimulatory effects of TPO with stem cell factor (SCF), interleukin-3 (IL-3), granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor were observed in both TPO-responding cases (9/17) and TPO-non-responding cases (8/13). In a leukaemic blast colony assay. significant growth response to TPO was observed in 5/6 CD7+ and 4/17 CD7-AML cases examined. However, the effect of TPO on the growth of CD7+ leukaemic blasts was not so potent as that of IL-3 and SCF, both of which support the proliferation of primitive haemopoietic progenitors. Expression of c-mpl (TPO receptor) was significantly higher in CD7+ AML cases than in CD7- cases, suggesting a relationship between expression of c-mpl and proliferative response to TPO. These data indicate that CD7+ leukaemic blasts express functional TPO receptors and proliferate in response to TPO. These observations also imply that CD7 expression on AML blasts may indicate involvement of leukaemic progenitors at an early stage of multipotent haemopoietic stem cells.
我们根据CD7和CD34的表面表达情况,研究了血小板生成素(TPO)对30例急性髓性白血病(AML)患者白血病原始细胞生长的影响:10例患者CD7阳性(CD7+),9例为CD7阴性/CD34阳性(CD7-/CD34+),其余11例为CD7阴性/CD34阴性(CD7-/CD34-)。采用3H-胸腺嘧啶核苷掺入法,在10/10例CD7+、5/9例CD7-/CD34+和2/11例CD7-/CD34-的AML病例中观察到白血病原始细胞对TPO有显著的生长反应。在TPO反应性病例(9/17)和TPO无反应性病例(8/13)中均观察到TPO与干细胞因子(SCF)、白细胞介素-3(IL-3)、粒细胞集落刺激因子和粒细胞-巨噬细胞集落刺激因子的协同刺激作用。在白血病原始细胞集落试验中,在检测的5/6例CD7+和4/17例CD7-AML病例中观察到对TPO有显著的生长反应。然而,TPO对CD7+白血病原始细胞生长的作用不如IL-3和SCF强,后两者均支持原始造血祖细胞的增殖。c-mpl(TPO受体)在CD7+AML病例中的表达明显高于CD7-病例,提示c-mpl表达与对TPO的增殖反应之间存在关联。这些数据表明,CD7+白血病原始细胞表达功能性TPO受体并对TPO产生增殖反应。这些观察结果还意味着AML原始细胞上的CD7表达可能表明白血病祖细胞参与了多能造血干细胞的早期阶段。