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Published on: October 23, 2019
MUM1/IRF4 expression in the circulating compartment of chronic lymphocytic leukemia
Fiona Craig1, Lorinda Soma, Melissa Melan
1Division of Hematopathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. craigfe@upmc.edu
Insights
MUM1/IRF4 expression in chronic lymphocytic leukemia (CLL) peripheral blood cells is highly variable. This heterogeneity suggests complex biology beyond current CLL models.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- MUM1/IRF4 is typically found in late germinal center/post germinal center B-cells.
- Previous studies on MUM1/IRF4 in chronic lymphocytic leukemia (CLL) have shown conflicting results regarding its prognostic significance.
- The role of MUM1/IRF4 in CLL pathobiology requires further investigation.
Purpose of the Study:
- To evaluate MUM1/IRF4 expression in peripheral blood CLL cells.
- To assess the correlation between MUM1/IRF4 expression and established CLL prognostic markers.
- To explore the implications of MUM1/IRF4 heterogeneity in CLL.
Main Methods:
- Analysis of MUM1/IRF4 expression in peripheral blood CLL cells using Histogel cell blocks.
- Quantification of MUM1/IRF4 staining intensity and proportion of positive cells.
- Correlation analysis with CD38, ZAP-70, and IgVH mutational status.
Main Results:
- MUM1/IRF4 was absent in 11% of CLL specimens.
- Variable intensity and proportion of MUM1/IRF4 positive cells were observed in the remaining cases (44% <20%, 33% 20-50%, 11% >50%).
- No significant correlation was found between MUM1/IRF4 expression and CD38, ZAP-70, or IgVH mutational status.
Conclusions:
- The variable expression of MUM1/IRF4 in CLL peripheral blood cells indicates significant biologic heterogeneity.
- This heterogeneity may not be captured by current binary models of CLL pathobiology.
- MUM1/IRF4's role in integrating lymphocyte activation pathways might contribute to CLL complexity.
Abstract:
MUM1/IRF4 is normally expressed in late germinal center/post germinal center B-cells. Previous studies of chronic lymphocytic leukemia in bone marrow and lymph node have demonstrated variable expression of MUM1/IRF4 and conflicting prognostic significance. In this study we evaluated MUM1/IRF4 expression in peripheral blood CLL cells utilizing Histogel cell blocks. MUM1/IRF4 was absent in 4/36 (11%) specimens. The remaining cases demonstrated variable intensity and proportion of positive cells: <20% positive 16/36 (44%), 20 - 50% positive 12/36 (33%), >50% 4/36 (11%). No correlation was identified between MUM1/IRF4 and percent of CD38 positive cells, CD38 status (+/-), ZAP-70 status (+/-), and IgVH mutational status. The variability in MUM1/IRF4 staining suggests a level of biologic complexity that is not adequately reflected in the current binary models of CLL pathobiology. This heterogeneity may reflect the role of MUM1/IRF4 as an effector and integrator of several lymphocyte activation pathways including antigenic and environmental stimuli.
