High-throughput sequencing of lymphoid receptor genes offers advantages over flow cytometry in assessing minimal residual disease for patients with T-lineage acute lymphoblastic leukemia/lymphoma.

T-lineage acute lymphoblastic leukemia/lymphoma (T-ALL) is an aggressive blood cancer that accounts for 20% to 30% of all acute leukemia. Choosing the correct treatment for a patient is difficult, with some suffering needless side effects from overtreatment and others facing the possibility of relapse because of insufficient treatment.

Harlan Robins, PhD, a computational biologist at Fred Hutchinson Cancer Research Center (Seattle, WA), and colleagues evaluated high-throughput sequencing (HTS) of lymphoid receptor genes as a way to diagnose T-ALL and assess patients for minimal residual disease (MRD), in which leukemia cells can still be detected in the bone marrow using sensitive tests (Sci Transl Med 2012;4:134ra63).

The current standard in the United States for assessing MRD is multiparametric flow cytometry; real-time quantitative PCR is another option. However, interpretation of flow cytometry data is highly subjective, the antibodies used are expensive, and the method is not very sensitive. Quantitative PCR, though highly sensitive, is expensive and labor intensive due to the need to develop patient-specific primers.

Robins and his colleagues used an Illumina Hi-Seq platform and proprietary analytic tools developed at the University of Washington and licensed exclusively to Adaptive Biotechnologies of Seattle, WA, to sequence the variable regions of the TCRB and TCRG T-cell antigen receptor genes in blood or bone marrow samples from 43 patients before treatment and at day 29 after treatment. They performed flow cytometry on all samples for comparison.

The HTS-based method identified clonal T-cell receptor sequence rearrangements in 31 of 43 pretreatment samples and recognized MRD in almost twice as many cases as flow cytometry. This suggests sequencing may detect MRD with higher sensitivity, giving patients a better chance to avoid relapse with additional treatment. “It’s just a matter of time before this makes it into the clinic,” Robins says. 

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