Expression of MUM1 in B Lymphoblastic Leukemia/Lymphoma, Burkitt Lymphoma, and T Lymphoblastic Leukemia/Lymphoma
Ellen F Krasik, Anne Deucher, Stephanie J McAlhany. University of California San Francisco, San Francisco, CA
Background: MUM1 (multiple myeloma 1) is a member of the interferon regulatory factor family (IRF4) of transcription factors that regulate expression of interferon and other cytokine-inducible genes. MUM1 is thought to work in conjunction with PU.1 as a transcriptional regulator in lymphoid cells, specifically in lymphocyte activation and terminal B-cell differentiation. MUM1 is overexpressed in a subset of mature B-cell lymphomas and plasma cell myelomas and can be expressed in activated T-cells. A prior investigation (Krasik and McAlhany, Mod Pathol 2012; 25:348A) focused on the expression of MUM1 in B lymphoblastic leukemia/lymphoma (B-ALL). In that retrospective review of initial-diagnosis B-ALL, MUM1 expression was detected in 10% of B-ALL and showed positive correlation with surface Ig expression but did not segregate by cytogenetic/molecular abnormality. Expression of MUM1 is not well characterized in T lymphoblastic leukemia/lymphoma (T-ALL/-LBL) or Burkitt lymphoma (BL), major differential diagnoses of B-ALL. We expand the earlier study to include cases of T-ALL/-LBL and BL and additional cases of B-ALL to investigate the utility of MUM1 in resolving this differential.
Design: A pathology specimen database search (approximately 14-year history) identified 81 cases of new-diagnosis B-ALL, 17 cases of new-diagnosis BL, and 22 cases of new-diagnosis T-ALL/-LBL. Formalin-fixed paraffin embedded tissue was stained using a MUM1 antibody with appropriate controls. Percentage of blasts positive for MUM1 and intensity of staining was recorded.
Results: MUM1 staining in B-ALL was seen in 7 cases (9%) with variable staining and percentage of positive blasts ranging from 10-80%. In BL, staining was seen 8 cases (47%) with weak to variable staining and percentage of positive blasts ranging from very focal to 80%. No staining for MUM1 was seen in any case of T-ALL/-LBL (0%). Patient distribution for B-ALL (46 male, 35 female) showed a mean age of 25 years (range 2-73 years). BL (12 male, 5 female) patients had a mean age of 27 years (range 4-69 years). For T-ALL/-LBL (19 male, 3 female) mean age was 24 years (range 2-76 years), and 6 (27%) presented as T-LBL and 16 (73%) as T-ALL.
Conclusions: The increased rate and intensity of expression of MUM1 in BL parallels the degree of B-cell lineage differentiation. In this data set, MUM1 staining is more frequent in BL yet is non-specific in the differential diagnosis with B-ALL. In addition, these findings suggest that MUM1 expression could be used to rule out a diagnosis of T-ALL/-LBL.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 237, Wednesday Morning