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. 2021 May 4;12:641692. doi: 10.3389/fimmu.2021.641692

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Copyright © 2021 Ouk, Roland, Gachard, Poulain, Oblet, Rizzo, Saintamand, Lemasson, Carrion, Thomas, Balabanian, Espéli, Parrens, Soubeyran, Boulin, Faumont, Feuillard and Vincent-Fabert

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Comparison of gene expression profile (GEP) of Myd88^L252P mice and patients with WM or other indolent B-cell NHL. Affymetrix differential gene expression profiles (GEP) between four Myd88^L252P mice (MUT, n=4) and three Cd19^Cre mice (WT, n=3) were compared to the Affymetrix GEP of purified bone marrow tumor B-cells from 11 WM patients with the MYD88^L265P mutation, resulting in selection of 462 probesets (319 genes). This selection was used on the Affymetrix transcriptome of an independent series of lymph node biopsies from 58 patients: 19 MYD88^wt chronic lymphocytic leukemias (CLL), 15 MYD88^L265P WM (WM_L265P), 12 MYD88^wt nodal marginal zone lymphomas (NMZL), 5 MYD88^wt WM with IgM peaks (WM_WT), 4 follicular lymphomas (FCL) and 3 patients with follicular hyperplasia (NT). (A) Hierarchical clustering and heatmap of the 462 selected probesets for mice (left), purified bone marrow MYD88^L265P WM B-cells (middle) and lymph nodes (right). Down and up-regulated genes are in blue and red respectively. Branches of down and up regulated genes in Myd88^L252P mice, MYD88^L265P WM bone marrow B-cells and MYD88^L265P WM lymph nodes are delineated by dashed lines. Venn diagrams of the intersections between the branches are shown, highlighting the consistency between branches across the different clustering. Some genes of interest are noted on the right. In bold are those of the plasma cell signature; *: genes in the predictor (see Figure 7B ); +: genes reported by Hunter et al. in WM (30); † : genes of the ABC/GC DLBCL signature (31). (B): Informativeness of MYD88^L265P WM diagnosis using the 462 selected probesets defined in Figure 8A . The 462 probesets defined from MYD88^L252P mice and bone marrow tumor B-cells from MYD88^L265P WM patients were used to predict MYD88^L265P WM diagnosis (WM^L265P versus non WM) from other lymphomas within the series of 58 lymph node biopsies. Probabilities that each sample belongs to WM^L265P versus non WM group are indicated. The WM^L265P versus non WM or not attributed (NA) assignment is shown on the left.