Next-Generation Sequencing Helped Identify Pathways for Transformation of WM to DLBCL

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IGHV analysis demonstrated that DLBCL tissue was clonally related to the antecedent WM clone.
IGHV analysis demonstrated that DLBCL tissue was clonally related to the antecedent WM clone.

Use of MYD88 L265P and immunoglobulin heavy chain variable region (IGHV) analysis was a safe, reliable, and accurate technique to help identify transformation of Waldenström macroglobulinemia (WM) to diffuse large B-cell lymphoma (DLBCL), according to a recent correspondence published in the British Journal of Haematology.1

In this analysis, the researchers looked at the clonal relationship of DLBCL and antecedent WM in 4 men with paired samples using MYD88 L265P and IGHV polymerase chain reaction and sequencing.

All 4 patients were treated with different chemotherapy regimens for WM and underwent high-dose chemotherapy protocols with or without transplant or central nervous system prophylaxis for DLBCL.

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And, results from the analysis showed that all 4 patients were heterozygous for the MYD88 L265P mutation on diagnostic WM samples. Patients 1, 2, and 4 also carried a heterozygous MYD88 L265P mutation at the time of transformation. Additionally, patients 2 and 3 had the same IGHV sequence as they had in the initial WM sample, “consistent with clonal evolution,” the researchers wrote.

Analysis of each patient's sample led to different results. For example, patient 1's sample showed IGHV4-34*01 and IGHV-69*03 in one-third of clones, interpreted as polyclonal. Patient 3 had wild-type alleles, which could be interpreted as synchronous lymphoma with clonal origin independent to the pretransformed WM, or loss of MYD88 L265P mutation during clonal evolution. The IGHV analysis indicated synchronous lymphoma with independent clonal origin.

Simultaneous IGHV analysis demonstrated that DLBCL tissue was clonally related to the antecedent WM clone and was synchronous to de novo B-cell lymphoma with independent clonal origin.

“This information is important for prognosis as de novo DLBCL has a better prognosis than transformed lymphoma,” the researchers wrote.

“We advocate the use of MYD88 L265P and IGHV analysis as a simple, reliable, and accurate technique to characterise transformation, even in centres where comprehensive genomic analysis is not available,” the researchers summarized.

Reference

  1. Talaulikar D, Biscoe A, Lin JH, et al. Genetic analysis of diffuse large B-cell lymphoma occurring in cases with antecedent Waldenström macroglobulinaemia reveals different patterns of clonal evolution [published online October 18, 2018]. Br J Haematol. doi:10.1111/bjh.15610

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