Axl expression is associated with adverse prognosis and with expression ofBcl-2 and CD34 in de novo acute myeloid leukemia (AML): results from a multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK)

Receptor tyrosine kinases (RTK) play a significant role in the signal trans duction of normal, and malignant hematopoietic cells. We have previously sh own that Axl, a novel RTK, is mainly expressed in leukemias of myeloid orig in, and that its expression may be associated with cells of monocytic origi n. Since expression of certain RTKs in cancer may be associated with differ ent biology and survival, we investigated whether the expression of Art is associated with clinical characteristics and survival in acute myeloid leuk emia (AML). RNA from 54 patients with AML treated in a cooperative group tr ial was analyzed in a retrospective and blinded manner using a semi-quantit ative reverse transcriptase polymerase chain reaction-based assay with prim ers specific for the Art gene. Axl expression was found in 19 out of the 54 cases (35%). Axl expression was not detected more frequently in patients o f older age, specific FAB categories, or cases with extramedullary disease. However, there existed a correlation between Art and bcl-2 expression leve ls. AML cells with high bcl-2 expression showed higher Axl expression (r = 0.32; P = 0.02), and furthermore, Art transcript numbers were also higher i n AWL with high CD34 expression (n = 38, r = 0.42; P = 0.008). No significa nt difference between leukemias expressing and not expressing Axl was found with regard to complete remission rate. However, quantitative Axl expressi on 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 m ultivariate Cox models adjusted for age, Auer rods and leukocyte counts. In conclusion, in this retrospective analysis, no difference with regard to c linical characteristics at diagnosis was found between AML patients whose l eukemia cells show Axl expression vs patients whose cells are Axl negative. The association between Axl and bcl-2 and Art and CD34 expression in de no vo AML needs further investigation. Similarly, the negative impact of Axi l evers on outcome should be confirmed in a larger cohort.