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A change in the signalling tail of part of the B-cell receptor that leaves the receptor switched on without needing anything to bind it. It marks a group of large B-cell lymphomas that depend on that signal, and therefore on the enzyme BTK.
The B-cell receptor signals through the ITAM motifs of CD79a and CD79b. In activated B-cell-like diffuse large B-cell lymphoma, the receptor signals continuously: the receptors form slow-diffusing clusters in the membrane like those of an antigen-stimulated normal B cell, and knocking down IgM, Ig-kappa, CD79A, CD79B or BTK kills the cell while leaving other lymphomas alone. Somatic mutations of the ITAM modules were detected frequently in activated B-cell-like biopsies, rarely in other diffuse large B-cell lymphomas and never in Burkitt or MALT lymphoma; the mutations raise surface receptor expression and blunt LYN, the kinase that normally damps the signal down (Davis 2010).
CD79B mutation with MYD88 L265P is what names the MCD genetic subtype (Schmitz 2018). CD79b protein itself is expressed on more than 95% of diffuse large B-cell lymphomas regardless of mutation status, which is why polatuzumab vedotin, the anti-CD79b conjugate, is given without a test.
In plain words · Part of the B-cell receptor found on nearly all B-cell lymphomas; the target of the ADC polatuzumab vedotin and a frequently mutated gene in brain and testicular lymphoma.
This result does not change a licensed treatment today. Together with MYD88 it puts a lymphoma in the group that has shown the most response to BTK inhibitor drugs in research studies, so it may make a trial relevant.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
Targeted sequencing of the CD79B ITAM region, reported as mutated or wild-type, usually as part of a lymphoma gene panel rather than alone. It is a different question from CD79b protein expression, which is near-universal in large B-cell lymphoma and is not tested before polatuzumab vedotin.
“In 18% of ABC DLBCLs, one functionally critical residue of CD79B, the first ITAM tyrosine, was mutated.”
Davis et al., Nature 2010No approval uses this readout as a threshold. It is defined by Schmitz et al., N Engl J Med 2018: genetics and pathogenesis of diffuse large B-cell lymphoma (574 biopsies; MCD, BN2, N1, EZB).
Shares LymphGen and the genetic clusters of large B-cell lymphoma, Next-generation sequencing (NGS), Comprehensive genomic profiling, Non-Hodgkin lymphoma (all types) and the tags biomarker, lymphoma.
Shares Cell of origin (GCB vs ABC), Non-Hodgkin lymphoma (all types), Diffuse large B-cell lymphoma and the tags biomarker, lymphoma.
Shares Next-generation sequencing (NGS), Comprehensive genomic profiling, Non-Hodgkin lymphoma (all types) and the tags biomarker, lymphoma.
Shares Next-generation sequencing (NGS), Non-Hodgkin lymphoma (all types), Diffuse large B-cell lymphoma and the tags biomarker, lymphoma.
Shares Non-Hodgkin lymphoma (all types), Diffuse large B-cell lymphoma and the tags biomarker, lymphoma.
Shares Non-Hodgkin lymphoma (all types), Diffuse large B-cell lymphoma and the tags biomarker, lymphoma.
Shares Non-Hodgkin lymphoma (all types) and the tags biomarker, lymphoma.
Shares B-cell receptor / BTK signalling (to NF-κB), BTK (Bruton tyrosine kinase), Ibrutinib, Next-generation sequencing (NGS) and the tags biomarker, lymphoma.