Expression of MUM1 in B Lymphoblastic Leukemia/Lymphoma
Ellen F Krasik, Stephanie J McAlhany. University of California, San Francisco, San Francisco, CA
Background: B lymphoblastic leukemia/lymphoma (B-ALL) is a neoplasm of precursor lymphoid cells committed to the B-cell lineage. Morphologically characterized as small to intermediate sized cells with scant cytoplasm and nuclei with dispersed chromatin and inconspicuous nucleoli, this leukemia affects children and adults typically involving marrow and peripheral blood. Immunophenotyping demonstrates virtually all cases to be positive for the B-cell marker CD19. Most cases express CD10, the blast marker TdT with variable expression of CD34. Most blasts are surface Ig negative. Subsets of B-ALL are defined by recurrent genetic abnormalities. MUM1 (multiple myeloma 1) is a member of the IRF (interferon regulatory factor) family of transcription factors that regulate expression of interferon-inducible genes. MUM1 is involved in B-cell differentiation and overexpressed in a subset of mature B-cell lymphomas. The expression of MUM1 in B-ALL is not characterized.
Design: A retrospective review of 68 consecutive cases at initial diagnosis of B-ALL was conducted; flow cytometry was preformed in all cases. Formalin-fixed paraffin-embedded tissue was stained using a MUM1 antibody. The percentage of positive blasts was recorded. Genetic changes were assessed using cytogenetic, FISH, and PCR studies.
Results: Positive MUM1 staining was seen in 7 of 68 cases (10%) with the percentage of positive blasts ranging from 10-80%. MUM1 positive blasts were seen in 4 female and 3 male patients, similar to the overall patient distribution (30 female, 38 male). The mean age of MUM1-positive B-ALL patients was 34 years (range 2-72 years), compared to the overall mean patient age of 23 years (range 4 months-72 years). Overall, the B-ALLs had an immunophenotype of CD19+ (68/68, 100%), CD10+ (60/68, 88%), CD34+ (60/68, 88%), TdT+ (64/68, 94%), and surface Ig- (61/68, 90%). MUM1-positive B-ALLs were more likely to be surface Ig positive (3/7, 43%) than MUM-1 negative cases (2/61, 3%). Genetic changes were assessed in 58 of 68 B-ALLs, and included recurrent genetic abnormalities t(9;22) (9 cases), hyperdiploidy (18 cases), hypodiploidy (3 cases), t(12;21) (5 cases), MLL rearrangement (5 cases), t(1;19) (2 cases); MUM-1 positive cases did not segregate with a particular genetic change.
Conclusions: MUM1 is expressed in a subset of B-ALL (10%) and positively correlates with surface Ig expression. As B-ALL exists along a spectrum of differentiation of B-lineage lymphoblasts from primarily surface Ig negative to rare surface Ig positive cases, this finding is compatible with the role of MUM1 in B-cell differentiation.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 236, Wednesday Afternoon