Graf Michaela, Reif Susanne, Kröll Tanja, Hecht Karin, Nuessler Volkmar, Schmetzer Helga
Medical Department 3, Klinikum Grosshadern, University of Munich, Munich, Germany.
Am J Hematol. 2006 Apr;81(4):227-35. doi: 10.1002/ajh.20526.
There is evidence to suggest, that cellular adhesion molecules and receptors could play a role in leukemia, e.g., through altered adhesive qualities of leukemic blasts. We have studied the expression of the beta2-integrin Mac-1 (CD11b) on mononuclear cells in 48 patients with AML at first diagnosis by flow cytometry using a direct fluorescein-conjugated antibody. A case was defined as positive if more than 20% of the cells expressed Mac-1. Within the FAB types, we observed a high expression rate in cases with M5 (100% MAC-1+ cases, 73% MAC-1+ cells), M4 (75% MAC-1+ cases, 48% MAC-1+ cells) and in cases with FAB-M1 with 71% MAC-1+ cases and 29% MAC-1+ cells. Separating our patients' cohort in cytogenetic risk groups, we could detect significant higher proportions of MAC-1+, cases (88% vs. 27%, P = 0.005) and cells (51% vs. 16%, P = 0.015) with poor cytogenetic risk compared to the favorable risk group. For clinical evaluations only patients treated according to the protocols of the German AML Cooperative Group (AML-CG) were included (n = 29, cases with AML-M3 were excluded). More MAC-1+ cases and cells were found in the "non-responders" group (n = 8) compared to the "responders" group (n = 24). We can conclude that AML cases with high MAC-1 expression are characterized by a worse prognosis. Evaluation of MAC-1 expression in AML might therefore contribute clinically important data with respect to develop new therapies that influence the interactions between integrins like MAC-1 on leukemic cells and endothelial or immunoreactive cells.
有证据表明,细胞粘附分子和受体可能在白血病中发挥作用,例如,通过白血病原始细胞粘附特性的改变。我们使用直接荧光素偶联抗体,通过流式细胞术研究了48例初诊急性髓系白血病(AML)患者单核细胞上β2整合素Mac-1(CD11b)的表达。如果超过20%的细胞表达Mac-1,则该病例被定义为阳性。在FAB分型中,我们观察到M5型病例(100% Mac-1阳性病例,73% Mac-1阳性细胞)、M4型病例(75% Mac-1阳性病例,48% Mac-1阳性细胞)以及FAB-M1型病例(71% Mac-1阳性病例,29% Mac-1阳性细胞)中Mac-1表达率较高。将我们的患者队列分为细胞遗传学风险组,与预后良好的风险组相比,我们发现细胞遗传学风险较差的组中Mac-1阳性病例(88%对27%,P = 0.005)和细胞(51%对16%;P = 0.015)的比例显著更高。仅纳入根据德国AML协作组(AML-CG)方案治疗的患者进行临床评估(n = 29,排除AML-M3病例)。与“缓解者”组(n = 24)相比,“无反应者”组(n = 8)中发现更多Mac-1阳性病例和细胞。我们可以得出结论,Mac-1高表达的AML病例预后较差。因此,评估AML中Mac-1的表达可能会为开发影响白血病细胞上如Mac-1等整合素与内皮细胞或免疫反应细胞之间相互作用的新疗法提供重要的临床数据。