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Chronic Lymphocytic Leukemia, IgVH Mutation Status

Chronic Lymphocytic Leukemia, IgVH Mutation Status

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Chronic Lymphocytic Leukemia, IgVH Mutation Status

  

Clinical Use

  • Assess prognosis for patients with chronic lymphocytic leukemia (CLL)

Clinical Background

CLL is the most common leukemia in the Western world. Patients with CLL follow heterogeneous clinical courses. Some survive for prolonged periods without definitive therapy, while others die rapidly, despite aggressive treatment. CLL patients can be divided into 2 basic groups on the basis of the mutational status of the immunoglobulin heavy-chain variable-region (IgVH ) gene in leukemic cells: patients with IgVH  gene mutations have longer survival than those without. Thus, mutation analysis may be useful for planning management strategies.

Two potential surrogate markers, CD38 and ZAP-70, have been investigated because of their association with lack of IgVH mutation, but the correlation is not 100%.

Method

This assay can be performed using either cells or plasma (Leumeta®). Following extraction of total RNA, the IgVH gene is amplified by reverse transcription-polymerase chain reaction and sequenced by dideoxy chain termination cycle sequencing with automated base calling. The nucleotide sequences are then aligned to NCBI IgBlast. A mutated status is assigned when there is 3% deviation from germline IgVH sequence. Sequencing may not be possible for specimens with <10% clonal B-cells.

Interpretive Information

A “mutated” result indicates 3% deviation from the germline sequence. Patients with IgVH mutations tend to have a more favorable prognosis, with longer overall survival.

 

This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. Performance characteristics refer to the analytical performance of the test.

Content reviewed 12/2012

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