He Qi, Li Xiao, Tao Ying, Liu Yi-Zhi, Yang Lian-Ping, Ying Shao-Xu
Department of Hematology, The Sixth Hospital, Shanghai 200233, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Jun;13(3):483-7.
To explore the expression of insulin-like growth factor receptor type I (IGF-IR) and its relationship to apoptosis in hematopoietic cells of MDS and AML marrow, bone marrow nucleated cells from 16 patients with myelodysplastic syndrome (MDS) and 16 patients with acute myeloid leukemia (AML) were collected for analysis, respectively. Another 16 normal donors' marrow samples were taken as controls. Immunocytochemical method (APAAP) and TdT-mediated dUTP nick end labeling (TUNEL) fluorescence were used simultaneously on cytospins of nucleated cells from these patients. Then, the ratios of IGF-IR positive cells and apoptosis cells in all nucleated cells were counted separately. The results showed that (1) there was a higher IGF-IR expression rate (56.8 +/- 14.3)% in nucleated cells of MDS marrow than that in normal marrow (40.4 +/- 9.6)% (P < 0.01). Also IGF-IR positive rate in AML marrow (86.8 +/- 13.8)% was significantly higher than that in normal marrow (P < 0.01). Furthermore, IGF-IR had higher expression in AML marrow when compared to MDS marrow (P < 0.01); (2) apoptosis in nucleated cells of MDS marrow (5.4 +/- 3.0)% was significantly higher than that in normal marrow (1.2 +/- 0.9)% (P < 0.01) and AML marrow (0.3 +/- 0.4)% (P < 0.01), while there was less apoptosis in AML marrow than that in normal marrow (P < 0.01); (3) apoptosis occurred mainly in IGF-IR negative cells (9.0 +/- 4.8)% and less in IGF-IR positive cells (1.4 +/- 2.4)% (P < 0.01). IGF-IR expression showed negative correlation with apoptosis (r = -0.852, P < 0.01); (4) IGF-IR of MDS nucleated cells in RAEB/RAEB-t/CMML expressed higher than that in RA/RAS (64.1 +/- 3.2% vs 53.5 +/- 16.2%) subgroup, although no significant difference was found (P > 0.05); and apoptosis in RAEB/RAEB-t/CMML subgroup was lower than that in RA/RAS cases (3.1 +/- 2.1% vs 6.4 +/- 2.8%) (P < 0.05); (5) IGF-IR positive rate in nucleated cells of MDS and AML marrow showed positive correlation with blast rate (r = 0.677; P < 0.01). It is concluded that there is overexpression of IGF-IR in marrow nucleated cells in MDS and AML cases. And it seems that the overexpression of IGF-IR may suggest some malignant proliferation tendency and suppress cell apoptosis through some mechanism in these malignant hematologic ailments. So, anti-IGF-IR will become a new approach for therapy of MDS and AML.
为探讨胰岛素样生长因子I型受体（IGF-IR）在骨髓增生异常综合征（MDS）和急性髓系白血病（AML）患者造血细胞中的表达及其与细胞凋亡的关系，分别收集16例MDS患者和16例AML患者的骨髓有核细胞进行分析。另取16例正常供者的骨髓样本作为对照。对这些患者有核细胞的细胞涂片同时采用免疫细胞化学方法（APAAP）和TdT介导的dUTP缺口末端标记（TUNEL）荧光法。然后，分别计数所有有核细胞中IGF-IR阳性细胞和凋亡细胞的比例。结果显示：（1）MDS骨髓有核细胞中IGF-IR表达率为（56.8±14.3）%，高于正常骨髓的（40.4±9.6）%（P<0.01）。AML骨髓中IGF-IR阳性率为（86.8±13.8）%，也显著高于正常骨髓（P<0.01）。此外，与MDS骨髓相比，AML骨髓中IGF-IR表达更高（P<0.01）；（2）MDS骨髓有核细胞凋亡率为（5.4±3.0）%，显著高于正常骨髓的（1.2±0.9）%（P<0.01）和AML骨髓的（0.3±0.4）%（P<0.01），而AML骨髓中的凋亡率低于正常骨髓（P<0.01）；（3）凋亡主要发生在IGF-IR阴性细胞（9.0±4.8）%，而IGF-IR阳性细胞中凋亡较少（1.4±2.4）%（P<0.01）。IGF-IR表达与凋亡呈负相关（r=-0.852，P<0.01）；（4）RAEB/RAEB-t/CMML亚组MDS有核细胞的IGF-IR表达高于RA/RAS亚组（64.1±3.2%对53.5±16.2%），但差异无统计学意义（P>0.05）；RAEB/RAEB-t/CMML亚组的凋亡率低于RA/RAS病例（3.1±2.1%对6.4±2.8%）（P<0.05）；（5）MDS和AML骨髓有核细胞中IGF-IR阳性率与原始细胞比例呈正相关（r=0.677；P<0.01）。结论：MDS和AML患者骨髓有核细胞中IGF-IR存在过表达。IGF-IR的过表达可能提示这些恶性血液病存在某种恶性增殖倾向，并通过某种机制抑制细胞凋亡。因此，抗IGF-IR将成为MDS和AML治疗的新途径。
