B-Cell Expression and B-Cell Gene Rearrangements in AML with t(8;21)(q22;q22)
Ryan C Johnson, Lisa Ma, Daniel A Arber, Tracy I George. Stanford University, Stanford, CA
Background: Aberrant B-cell marker expression is present in acute myeloid leukemia (AML) with t(8;21)(q22;q22). It is hypothesized that B-cell marker expression is influenced by transcription factor activation (e.g. PAX5) which has been similarly shown to be overexpressed in a subset of t(8;21) AML. We characterized a series of cases of t(8;21) AML for B-cell expression via immunohistochemistry, flow cytometry, and B-cell gene rearrangements.
Design: 44 patients (age range 5-68 years) with t(8;21) AML were identified from our institutional database from 1990 to 2011 with diagnostic bone marrow specimens. Specimens were examined by flow cytometry using standard techniques with antibodies directed against standard myelocytic, monocytic, B-lymphocytic, and T/NK-lymphocytic panel antigens (FACSCanto II; Becton Dickinson Biosciences, San Jose, CA): positive expression and partial positive expression were defined at >20% and 10-20%, respectively. Immunohistochemical staining via automated platforms (Ventana Benchmark, Tucson, AZ) and antibodies to PAX5, OCT-2, and BOB.1 (DAKO, Carpinteria, CA) were performed on available bone marrow core biopsy samples. Polymerase chain reaction (PCR) amplification of IgH and IgK were performed and directly sequenced to evaluate for rearrangements.
Results: B-lymphocytic antigen flow cytometry data showed that 20 of 22 (90.9%) cases demonstrated positivity/partial positivity for CD19, and 4 of 16 (25%) demonstrated positivity/partial positivity for cCD79a. 18 of 32 (56.2%) cases demonstrated weak to moderate PAX5 expression, and 5 of 15 (33.3%) cases expressed OCT-2 expression. CD20, CD22, and BOB.1 were negative in all cases assessed. All cases positive for OCT-2 expression were positive for PAX5; similarly all cases expressing cCD79a demonstrated PAX5 expression. However, PAX5 positivity did not necessarily correlate with cCD79a or OCT-2 expression. One of 19 cases of AML with t(8;21) contained a B cell gene rearrangement.
Conclusions: This is one of the largest studies assessing for B-cell expression and rearrangement in cases of t(8;21) AML to date. A significant proportion of cases expressed B-cell markers CD19, CD79a and PAX5, with a smaller proportion of cases demonstrating OCT-2 expression. CD19, cCD79a, and OCT-2 expression were highly correlated with PAX5 expression, but PAX5 expression did not necessarily predict cCD79a or OCT-2 expression. Additionally, one case demonstrated an IgH rearrangement. These findings shed additional light on the relationship between B-cell marker expression and rearrangements in t(8;21) AML.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 208, Tuesday Morning