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The reason that a certain subgroup of acute myeloid leukemia (AML) patients with t(8;21) translocation (generating the  AML1/ETO  fusion gene) displays a poor survival remains elusive. The proto-oncogene  c-kit  is expressed in approximately 80% of AML cases. The kinase domain mutation of the  c-kit  gene, one of the most common gain-of-function mutations associated with t(8;21) AML, predicts higher relapse risk and poor prognosis. However, the role of  c-kit  high expression in t(8;21) AML remains poorly understood. Here we evaluated the prognostic significance of  c-kit  expression levels in AML patients. The mRNA expression of  c-kit  was determined by real-time quantitative reverse transcription PCR in 132 adult AML patients. Patients were grouped into quartiles according to  c-kit  expression levels (Q1–Q4, each quartile containing 25% of patients) and divided into  c-kit  high (Q4; n = 33) and  c-kit  low (Q1–Q3; n = 99). High  c-kit  expression was associated with  AML1/ETO- positive and with  c-kit  mutation. Of note, 35.8% of the  AML1/ETO- positive AML patients carrying wild-type  c-kit  expressed high levels of  c-kit , suggesting that other factors are involved in  c-kit  overexpression. High  c-kit  expression was associated with inferior overall and event-free survival in  AML1/ETO- positive patients and was independently predictive for overall and event-free survival in multivariate analyses in a  c-kit  mutation-independent manner. Thus, high  c-kit  expression serves as a reliable molecular marker for poor prognosis, supporting a pathogenetic role of  c-kit  signaling in  AML1/ETO- positive AML.  AML1/ETO- positive patients with high  c-kit  expression might benefit from early treatment modifications and molecular target therapies.

High Expression of c-kit mRNA Predicts Unfavorable Outcome in Adult Patients with t(8;21) Acute Myeloid Leukemia