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Magic™ TCR Repertoire Analysis for Minimal Residual Disease Quantification

Creative Biolabs is able to provide the service of minimal residual disease (MRD) quantification for our customers all over the world. According to our Magic™ platform which mainly based on next generation sequencing (NGS) technique, we can quantify MRD accurately and efficiently.

MRD is the name given to small numbers of leukemic cells or other cancer cells that remain in the patient during treatment or after treatment when the patient is in remission. It is the major cause of relapse in cancer and leukemia. In cancer treatment, particularly leukemia, MRD quantification is significantly important, such as determining whether treatment has wiped out cancer, comparing the efficacy of different treatments as well as detecting recurrence of cancer. Several studies have confirmed the importance of assessing MRD to predict clinical outcomes of patients. Detection of increasing MRD may permit early intervention to prevent clinical relapse. However, MRD quantification remains an uncommon diagnostic test because of logistical and financial barriers to be widely used.

Current clinical strategies to assess MRD include multiparametric flow cytometry (mpFC) and quantitative polymerase chain reaction (PCR)-based methods. mpFC typically permits detection of recurrent disease, but the sensitivity of the result is rather low. In addition, the data interpretation is operator-dependent and laborious, consequently poorly standardized. Furthermore, variable expression of leukemic antigens in the post-therapy setting mystify MRD detection by mpFC. Molecular-based methods for detection of MRD can achieve good sensitivity. However, real-time quantitative PCR-based assays using patient-specific primers are expensive, labor-intensive, and difficult to implement uniformly. High-throughput next-generation sequencing (NGS) is an emerging technology which can provide insight into the complexity of the adaptive immune response by analyzing lymphoid receptor gene rearrangement. Thus, NGS of lymphoid TCR gene repertoire may improve clinical diagnosis and subsequent MRD monitoring of lymphoproliferative disorders.

The role of minimal residual disease and leukemic stem cells in the emergence of relapse (Zeijlemaker & Schuurhuis 2013). Fig.1 The role of minimal residual disease and leukemic stem cells in the emergence of relapse (Zeijlemaker & Schuurhuis 2013).

At acute myeloid leukemia diagnosis, a heterogeneous population of cells often coexist, including different subpopulations of leukemic stem cells. MRD assessment focuses on the detection of leukemic cells present after treatment. Different subpopulations of chemotherapy resistant leukemic stem cells can grow out and cause relapse.

Creative Biolabs has applied our advanced Magic™ TCR repertoire analysis platform to MRD quantification for highly accurate and reproducible results. The variable regions were sequenced through our Magic™ platform. Polymerase chain reaction targets all potential V(D)J rearrangement combinations. We use pretreatment samples to define complementarity determining region 3 (CDR3) sequences, and paired post-treatment samples to evaluate for MRD. Our method requires no per-patient customization, thus combining the benefits of high sensitivity and universal applicability. To achieve accurate MRD quantification, Creative Biolabs also developed a systematic bioinformatics methodology to aggregate cancer clone sequence variants arising from systematic and random artifacts occurring during NGS.

Advantages of MRD quantification service including but not limited to:


Scientists of Creative Biolabs have extensive experience in minimal residual disease quantification. They are confident in providing our clients with the best service at the most competitive cost.

For more detailed information, please feel free to contact us or directly send us an inquiry.

References

  1. Wu, D.; et al. High-throughput sequencing detects minimal residual disease in acute T lymphoblastic leukemia. Science translational medicine. 2012, 4(134):134ra63-134ra63.
  2. Zeijlemaker, W.; Schuurhuis, G.J. Minimal residual disease and leukemic stem cells in acute myeloid leukemia, Leukemia. InTech. 2013.



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