T-Cell Receptor Gene Rearrangement, PCR, Bone Marrow
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The T-cell receptor (TCR) genes (alpha, beta, delta, and gamma) are comprised of numerous, discontinuous coding segments that somatically rearranged to produce heterodimeric cell surface T-cell receptors, either alpha/beta (90%-95% of T cells) or gamma/delta (5%-10% of T cells). With rare exceptions (eg, some neoplastic B-lymphoid proliferations), other cell types retain the "germline" configuration of the TCR genes without rearrangement.
The marked diversity of somatic TCR-gene rearrangements is important for normal immune functions, but also serves as a valuable marker to distinguish abnormal T-cell proliferations from reactive processes. A monoclonal expansion of a T-cell population will result in the predominance of a single TCR-gene rearrangement pattern. In contrast, reactive T-cell expansions are polyclonal (or multiclonal), with no single clonotypic population predominating in the population of T cells. These distributive differences in both TCR sequence and genomic rearrangement fragment sizes can be detected by molecular techniques (ie, PCR) and used to determine if a population of T cells shows monoclonal or polyclonal features.
Determining whether a T-cell population is polyclonal or monoclonal
An interpretive report will be provided. Results will be characterized as positive, negative, or indeterminate for a clonal T-cell population.
In the appropriate clinicopathologic setting, a monoclonal result is associated with a neoplastic proliferation of T cells (see Cautions).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
To determine the significance of the result, it must always be interpreted in the context of other clinicopathologic information.
The interpretation of the presence or absence of a predominant T cell receptor (TCR)-gene rearrangement profile is sometimes subjective.
The detection of a clonal TCR-gene rearrangement by this test is not necessarily synonymous with the presence of a T-cell neoplasm. False-positive results can occur because of the sensitivity of PCR technique and the problem of nonuniform (skewed) amplification of target T-cell gene rearrangements. The latter problem can occur when the total T-cell number in a sample is limited, or because of physiologic skewing of the T-cell repertoire as seen with ageing, posttransplantation, or T-cell reactions in autoimmune or (nonlymphoid) malignancies. False-negative results can occur for many reasons, including tissue sampling, poor amplification, or failure to detect a small minority of T-cell gene segment rearrangements with the use of consensus PCR primers. In some cases, an indeterminate or equivocal result will occur because the pattern of gene rearrangements is abnormal (compared to typical polyclonal T-cell processes), but not definitive, for a monoclonal T-cell population. In these situations, distinction of a small monoclonal subpopulation from an over-represented, but reactive, population may not be possible.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Positive, negative, or indeterminate for a clonal T-cell population
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Liu H, Bench AJ, Bacon CM, et al: A practical strategy for the routine use of BIOMED-2 PCR assays for detection of B- and T-cell clonality in diagnostic haematopathology. Br J Haematol 2007;138(1):31-43
2. Van Krieken JH, Langerak AW, Macintyre EA, et al: Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia 2007;21(2):201-206
3. Bruggermann M, White H, Gaulard P, et al: Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies Report of the BIOMED-2 Concerted Action BHM4 CT98-3936. Leukemia 2007;21(2):215-221