title: Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia.
abstract: ETV6 is an important hematopoietic regulatory factor and ETV6 gene rearrangement is involved in a wide variety of hematological malignancies. In this study, we sought to investigate the incidence of ETV6-associated fusion genes in B- and T-lineage acute lymphoblastic leukemia (ALL) by multiplex-nested reverse transcription-polymerase chain reaction (RT-PCR) in 176 adult ALL patients. Total RNA was extracted from bone marrow samples of ALL patients including 136 B- and 40 T-lineage ALL, and ETV6 fusion genes were detected by multiplex-nested RT-PCR. Changes of ETV6 fusion gene mRNA transcript levels were examined by real-time RT-PCR. We detected a total of 15 ETV6 gene rearrangements with a positive rate of 8.5%, involving seven ETV6-associated fusion genes in 13 B-ALL (13/136, 9.6%) and 2 T-ALL patients (2/40, 5.0%). ETV6-RUNX1 were observed in six cases (3.4%), ETV6-JAK2 in three cases (1.7%), ETV6-ABL1 in two cases (1.1%), and ETV6-ABL2, ETV6-NCOA2, ETV6-SYK, and PAX5-ETV6 each in one case (0.6%). ETV6-JAK2 was found in both B-ALL and T-ALL patients. Furthermore, real-time quantitative RT-PCR assays showed that the ETV6-RUNX1 mRNA transcript levels decreased during conventional chemotherapy or hematopoietic stem cell transplantation. This study shows that multiplex-nested RT-PCR is an effective and accurate tool to identify ETV6 rearrangements in adult ALL, which provides some clues into the diagnosis and prognosis of ALL but also molecular markers for the detection of minimal residual disease in adult ALL.
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors.forename: Min-hang
authors.initials: MH
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Jing
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Mian-yang
authors.initials: MY
authors.lastname: Li
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Han
authors.forename: Jun-zhong
authors.initials: JZ
authors.lastname: Sun
authors.forename: Li-li
authors.initials: LL
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation / Q000502:physiology; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic / Q000502:physiology; D055815:Young Adult; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein