Using cell-free RNA to identify B- and T-cell clonality for diagnosis and monitoring of B- and T-cell neoplasms

Cell-free RNA (cfRNA) is emerging as a supplemental approach for liquid biopsy (LBx). Given that lymphoid cells and plasma cells express substantial quantities of immunoglobulin (Ig) and T-cell receptor (TCR) RNA, we investigated the utility of using cfRNA for detecting B-cell and T-cell clonality in LBxs. Using next-generation sequencing (NGS) of cfRNA, we clonotyped Igs and TCRs in LBx samples from patients with B-cell neoplasm, T-cell neoplasm, myeloid neoplasm and solid tumors alongside cancer-free individuals. To establish a clonality cutoff, we clonotyped tissue RNA from patients with confirmed clonal B- or T-cell and from polyclonal. Clonotype-naïve testing of LBx samples demonstrated B-cell clonality in 36% of B-cell neoplasms, 7% of normal, 8% of T-cell lymphomas, 13% of myeloid neoplasms, and 14% of solid tumors. T-cell clonality using TCR beta or gamma demonstrated T-cell clonality in 22% of T-cell neoplasms, 3% of normal, 5% of myeloid neoplasms, 7% of solid tumors and 3% of B-cell neoplasms. This confirms that Clonotype-naïve cfRNA testing in LBx is a reliable approach for detecting B- and T-cell clonality.