title: Development of a biochip-based assay integrated in a global strategy for identification of fusion transcripts in acute myeloid leukemia: a work flow for acute myeloid leukemia diagnosis.
abstract: Three major types of rearrangements are involved in acute myeloid leukemias (AML): t(8;21)(q22;q22), inv(16)(p13q22), and 11q23/MLL abnormalities. Their precise identification becomes essential for diagnosis, prognosis, and therapeutic choices. Resulting fusion transcripts (FT) are also powerful markers for monitoring the efficacy of treatment, the minimal residual disease (MRD) and could become therapeutic targets. Today, the challenge is to propose an individual follow-up for each patient even for those with a rare fusion event. In this study, we propose a biochip-based assay integrated in a global strategy for identification of rare FT in AML, after fluorescence in situ hybridization detection, as described by the World Health Organization classification. Using cell lines, we developed and validated a biochip-based assay called the AMLFusionChip that identifies every FT of AML1-ETO, CBFbeta-MYH11 as well as MLL-AF9, MLL-ENL, MLL-AF6, and MLL-AF10. The original design of our AMLFusionChip.v01 enables the identification of these FT wherever the breakpoint on the partner gene may be. In case of biochip negative result, our 3'RACE amplification strategy enables to clone and then sequence the new translocation partner. This AMLFusionChip strategy fits into the concept of personalized medicine for the largest number of patients.
authors.affiliation: Service d' Anatomie et Cytologie Pathologiques, CHU Nord, Boulevard Pierre Dramard, Marseille Cedex 20, France. sophie.giusiano@ap-hm.fr
authors.forename: S
authors.initials: S
authors.lastname: Giusiano
authors.forename: C
authors.initials: C
authors.lastname: Formisano-Tréziny
authors.forename: A
authors.initials: A
authors.lastname: Benziane
authors.forename: N
authors.initials: N
authors.lastname: Maroc
authors.forename: C
authors.initials: C
authors.lastname: Picard
authors.forename: F
authors.initials: F
authors.lastname: Hermitte
authors.forename: C
authors.initials: C
authors.lastname: Taranger-Charpin
authors.forename: J
authors.initials: J
authors.lastname: Gabert
mesh_terms: D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic
chemical_list: C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase