Yoshiko Hashii
Osaka university, Japan
Biography:
Yoshiko Hashii is a associate professor Department of Pediatrics, Osaka University Japan.
Abstract:
Objective: Monitoring minimal residual disease (MRD) is important in predicting a patient’s disease relapse and optimizing the treatment strategy. We investigated the clinical significance of WT1 mRNA as an MRD monitoring marker in ALL patients by measuring the PB and BM WT1 mRNA levels in childhood and adult ALL patients. Method: Peripheral blood (PB) and bone marrow (BM) samples were collected from 49 subjects of untreated childhood ALL from Dec. 2014 to Dec. All of pediatric patients received the JPLSG ALL-B12 protocol. 2015. The WT1 mRNA levels were measured using RT-qPCR based assay; WT1 mRNA Assay kit II "OTSUKA". As an MRD monitoring marker we measured and assessed the quantification of fusion gene transcript and immunoreceptor gene rearrangements. Results: This study enrolled 49 patients with de novo childhood acute lymphoblastic leukemia (ALL) and 19 adult patients with ALL. WT1 mRNA showed high positive expression rates of 90% or more in ALL patients, and fusion gene transcripts were detected in 22.4% of childhood ALL cases prior to treatment. During follow-up at 4-6 months, WT1 mRNA levels in childhood ALL cases were observed to be lower in patients undergoing hematological remission after treatment when compared to the initial stages. We also assessed hematological remission via ROC analysis. The upper cut-off values were calculated to be 220 and 1,820 copies/µg RNA in the peripheral blood (PB) and bone marrow (BM) samples, respectively. Since 50 copies/µg RNA was determined to be both, the limit of detection (LOD) and minimal residual disease (MRD) threshold, WT1 mRNA regions below the upper cut-off values indicated remission depth. The detection of high WT1 mRNA levels, even in patients without fusion gene transcripts, reflected the treatment effects and remission depth, demonstrating its capacity to be a useful MRD monitoring marker in ALL.