The human androgen receptor X-chromosome inactivation assay for clonality diagnostics of natural killer cell proliferations

Abstract

Clonality is a frequently exploited characteristic of lymphoid malignancies. However, in the natural killer (NK) cell subset of large granular lymphocyte proliferations, clonality is difficult to prove because of the lack of specific genetic markers, such as immunoglobulin or T-cell receptor gene rearrangements. The human androgen receptor (HUMARA) assay, a polymerase chain reaction-based X-chromosome inactivation assay, is a potential diagnostic tool in these disorders. Although there is much experience with X-chromosome inactivation assays in myeloid proliferations, these assays have found only very limited application in clonality assessment of NK cell proliferations. We applied the HUMARA assay in laboratory diagnostics for detection of clonality in NK cell proliferations. We describe its test performance and report three cases in which clonality of NK cell populations was investigated by use of this assay. Our results demonstrate the usefulness of the HUMARA assay in the diagnostic workup of NK cell proliferations.

Figure 1

Result of the HUMARA assay for patient in case 2. Results are representative for the other cases. Calculations of the ratios are presented in Table 1.