journal contribution
posted on 2023-03-31, 21:27 authored by Mu Hao, Bart Barlogie, Guido Tricot, Lanting Liu, Lugui Qiu, John D. Shaughnessy, Fenghuang Zhan <p>Supplemental Data: four Tables and one Figure Supplement Table 1. B-cell markers and differentiation-related genes in WM, MM, and their normal counterparts Supplement Table 2. Most differentially expressed genes (n = 55) allowing the distinction of WM-BC from PB-BC and T-BC Supplement Table 3. Most differentially expressed genes (n = 46) allowing the distinction of WM-PC from T-PC and N-PC Supplemental Table 4. Clinical information of WM patients used for the Figure 4 Supplemental Fig. 1: Immunofluorescence shows CD3 expression (Green) on normal T cells and CD19 expression (Red) on normal B cells derived from peripheral blood of a healthy donor. DAPI (blue color) was used to stain cell nuclei.</p>
Funding
NIH
National Natural Science Foundation of China
History
ARTICLE ABSTRACT
That the malignant clone of Waldenström's macroglobulinemia (WM) demonstrates significant intraclonal heterogeneity with respect to plasmacytoid differentiation indicates the mechanistic complexity of tumorigenesis and progression. Identification of WM genes by comparing different stages of B cells may provide novel druggable targets.
The gene expression signatures of CD19+ B cells (BC) and CD138+ plasma cells (PC) from 19 patients with WM were compared with those of BCs from peripheral blood and tonsil and to those of PCs from the marrow of healthy (N-PC) and multiple myeloma donors (MM-PC), as well as tonsil (T-PC). Flow cytometry and immunofluorescence were used to examine T-cell marker expression on WM tumor cells.
Consistent with defective differentiation, both BCs and PCs from WM cases expressed abnormal differentiation markers. Sets of 55 and 46 genes were differentially expressed in WM-BC and WM-PC, respectively; and 40 genes uniquely dysregulated in WM samples were identified. Dysregulated genes included cytokines, growth factor receptors, and oncogenes not previously implicated in WM or other plasma cell dyscrasias. Interestingly, strong upregulation of both IL6 and IL6R was confirmed. Supervised cluster analysis of PC revealed that marrow-derived WM-PC was either MM-PC–like or T-PC–like, but not N-PC–like. The aberrant expression of T-cell markers was confirmed at the protein level in WM-BC.
We showed that comparative microarray profiles allowed gaining more comprehensive insights into the biology of WM. The data presented here have implications for the development of novel therapies, such as targeting aberrant T-cell markers in WM.
