Rochlitz C, Lohri A, Bacchi M, Schmidt M, Nagel S, Fopp M, Fey M F, Herrmann R, Neubauer A
Abteilung für Onkologie, Kantonsspital Basel, Switzerland.
Leukemia. 1999 Sep;13(9):1352-8. doi: 10.1038/sj.leu.2401484.
Receptor tyrosine kinases (RTK) play a significant role in the signal transduction of normal, and malignant hematopoietic cells. We have previously shown that Axl, a novel RTK, is mainly expressed in leukemias of myeloid origin, and that its expression may be associated with cells of monocytic origin. Since expression of certain RTKs in cancer may be associated with different biology and survival, we investigated whether the expression of Axl is associated with clinical characteristics and survival in acute myeloid leukemia (AML). RNA from 54 patients with AML treated in a cooperative group trial was analyzed in a retrospective and blinded manner using a semi-quantitative reverse transcriptase polymerase chain reaction-based assay with primers specific for the Axl gene. Axl expression was found in 19 out of the 54 cases (35%). Axl expression was not detected more frequently in patients of older age, specific FAB categories, or cases with extramedullary disease. However, there existed a correlation between Axl and bcl-2 expression levels. AML cells with high bcl-2 expression showed higher Axl expression (r = 0.32; P = 0.02), and furthermore, Axl transcript numbers were also higher in AML with high CD34 expression (n = 38, r = 0.42; P = 0.008). No significant difference between leukemias expressing and not expressing Axl was found with regard to complete remission rate. However, quantitative Axl expression was associated with worse progression-free and overall survival. Higher Axl levels had worse prognosis for progression-free (beta: 0.68, s.e.: 0.28, P = 0.015) and overall survival (beta: 0.61, s.e.: 0.31, P = 0.05) using multivariate Cox models adjusted for age, Auer rods and leukocyte counts. In conclusion, in this retrospective analysis, no difference with regard to clinical characteristics at diagnosis was found between AML patients whose leukemia cells show Axl expression vs patients whose cells are Axl negative. The association between Axl and bcl-2 and Axl and CD34 expression in de novo AML needs further investigation. Similarly, the negative impact of Axl levels on outcome should be confirmed in a larger cohort.
受体酪氨酸激酶（RTK）在正常和恶性造血细胞的信号转导中发挥着重要作用。我们之前已经表明，新型RTK Axl主要在髓系起源的白血病中表达，并且其表达可能与单核细胞起源的细胞有关。由于癌症中某些RTK的表达可能与不同的生物学特性和生存率相关，我们研究了Axl的表达是否与急性髓系白血病（AML）的临床特征和生存率相关。使用针对Axl基因的特异性引物，通过基于半定量逆转录聚合酶链反应的检测方法，以回顾性和盲法对在一项合作组试验中接受治疗的54例AML患者的RNA进行了分析。在54例病例中有19例（35%）检测到Axl表达。在老年患者、特定FAB分型或有髓外疾病的病例中，未更频繁地检测到Axl表达。然而，Axl与bcl-2表达水平之间存在相关性。bcl-2高表达的AML细胞显示出更高的Axl表达（r = 0.32；P = 0.02），此外，在CD34高表达的AML中Axl转录本数量也更高（n = 38，r = 0.42；P = 0.008）。在完全缓解率方面，表达和不表达Axl的白血病之间未发现显著差异。然而，Axl的定量表达与无进展生存期和总生存期较差相关。使用针对年龄、Auer小体和白细胞计数进行调整的多变量Cox模型，较高的Axl水平对无进展生存期（β：0.68，标准误：0.28，P = 0.015）和总生存期（β：0.61，标准误：0.31，P = 0.05）具有更差的预后。总之，在这项回顾性分析中，白血病细胞显示Axl表达的AML患者与细胞为Axl阴性的患者在诊断时的临床特征方面未发现差异。Axl与bcl-2以及Axl与初发AML中CD34表达之间的关联需要进一步研究。同样，Axl水平对预后的负面影响应在更大的队列中得到证实。
