Genomic analysis for TIM-3-expressing measurable residual disease post allogeneic SCT

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  • Sakoda Teppei
    Center for Cellular and Molecular Medicine, Kyushu University Hospital

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  • 急性骨髄性白血病におけるTIM-3をマーカーとした同種移植後微小残存病変のゲノム解析

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<p> The relapse of acute myeloid leukemia is a critical problem in clinics. As the prognosis of patients who relapse after allogeneic stem cell transplantation (allo-SCT) is poor, the evaluation of minimal/measurable residual disease (MRD) is crucial for determining the risk of relapse. Multiparameter flow cytometry (MFC) is an established method for quantifying MRD by European Leukemia Net. One of our primary concerns about MFC-MRD is its genetic backbone. In addition to MFC, detecting genetic abnormalities with next-generation sequencing (NGS) is a useful method for quantifying MRD. MFC-MRD and NGS-MRD are complementary approaches for predicting relapse, but conflicting results are observed in some cases. To determine the relevance of MFC-MRD and NGS-MRD, we performed single-cell targeted DNA and surface protein analysis using the Tapestri platform. Then, we established a heterogeneity characterized by the expression pattern of the surface antigen where populations with similar genetic background could produce different MRD statuses between MFC-MRD and NGS-MRD. Therefore, to track the residual disease responsible for relapse, we focused on T-cell immunoglobulin mucin-3 (TIM-3), a leukemic stem cell (LSC)-specific functional molecule. Furthermore, we demonstrated that the evaluation of TIM-3+ LSCs could be useful in predicting relapses after allo-SCT.</p>

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