Orphan receptor ROR1 for detection of minimal residual disease in chronic lymphocytic leukemia

Background and Aims. The detection of minimal residual disease (MRD) of chronic lymphocytic leukemia (CLL) using multicolor flow cytometry has been widely used in clinical studies to evaluate the effectiveness of treatment. The method is being improved by searching for the most sensitive and specific markers for use in panels for 6–8 color cytometers. According to published data, ROR1 shows high expression on CLL cells, and lack of expression on mature lymphocytes, which distinguishes it from other markers used to detect MRD in CLL.

Aim: to determine a significance of ROR1 for detection of MRD CLL by flow cytometry in a 4-color panel.

Materials and Methods. We analyzed 64 bone marrow samples of 37 patients with a verified diagnosis of CLL after the 3rd and 6th cycles of therapy according to bendamustine and rituximab (BR) regimen – 15 MRD-negative and 49 MRD-positive. Quantitative determination of MRD was carried out by the standardized method of 4-color flow cytometry according to the recommendations of ERIC (European research initiative on CLL) with the inclusion of ROR1 in the diagnostic panel. A discriminatory analysis of the differentiating properties of diagnostic markers was performed using Statistica 10.

Results. ROR1 has demonstrated high differentiating properties on CLL cells and mature lymphocytes. All the analyzed samples showed a bright monomorphic expression of ROR1 on CLL cells and B-cell precursors, and the absence of its expression on mature lymphocytes.

Conclusion. ROR1 is a highly specific and sensitive marker for the detection of CLL cells among mature lymphocytes. The high expression of ROR1 on normal B-cell precursors requires the use of ROR1 in combination with a marker that differentiates CLL cells from progenitor cells (CD81).

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