When should I order gene studies to establish clonality and rule out B-cell lymphoproliferative processes?

Attending, Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York

This month, Carol S. Portlock, MD, advises on gene studies to establish clonality in B-cell lymphoproliferative disorders.

CLINICAL DILEMMA

I perform T-cell receptor gene studies to establish clonality if abnormalities in the T-cell population are detected. Do I need to order both beta and gamma analyses? I frequently order flow cytometry to establish clonality and to rule out B-cell lymphoproliferative processes. When do I need to order immunoglobulin heavy chain (IgH) gene rearrangement by fluorescent polymerase chain reaction?

EXPERTS MAKE THE CALL

You are correct that generally IgH gene rearrangement is not needed to define B-cell clonality – given that flow cytometry demonstrates clonality simply through an abnormal kappa-lambda immunoglobulin light chain ratio.

There are certain cases where, if needed, IgH gene rearrangement can be performed; for example, if flow cytometric instrumentation is

not available or if the amount of tissue for a sample is limited. Then, IgH gene rearrangement may be used to establish the clonal relationship between an initial disease presentation and relapse or transformation.

Recently, advances in T-cell flow cytometry with multi-parameter flow technology have improved detection of T-cell clonality and monitoring minimal residual disease following therapy. T-cell clonality can be established by using a kit to interrogate Vβ repertoire of T-cells.

Typically, though, the gold standard for establishing clonality is performing a molecular assay for T-cell receptor– (TCR-) beta and gamma gene rearrangements.

Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.

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