title: High expression of c-kit mRNA predicts unfavorable outcome in adult patients with t(8;21) acute myeloid leukemia.
abstract: 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.
authors: Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
authors: Xiaoning
authors: X
authors: Gao
authors: Institute of Basic Medicine, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
authors: Ji
authors: J
authors: Lin
authors: Department of Hematology, China-Japan Friendship Hospital, Beijing, China.
authors: Li
authors: L
authors: Gao
authors: Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
authors: Ailing
authors: A
authors: Deng
authors: Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
authors: Xiaolin
authors: X
authors: Lu
authors: Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
authors: Yonghui
authors: Y
authors: Li
authors: Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
authors: Lili
authors: L
authors: Wang
authors: Department of Hematology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.
authors: Li
authors: L
authors: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015331:Cohort Studies; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D014178:Translocation, Genetic; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; C000715470:MAS1 protein, human; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000075142:RUNX1 Translocation Partner 1 Protein; D019009:Proto-Oncogene Proteins c-kit