Dysregulated Expression of Transcription Factor PU. 1 (Sfpi1) in Pre-B-Cell Acute Lymphoblastic Leukemia/Lymphoma Is Associated with Aggressive Clinical Course
I Mirza, A Surmawala, A Szkotak, E Torlakovic, A Mansoor. University of Alberta, Edmonton, AB, Canada; University of Saskatchewan, Saskatoon, SK, Canada; University of Calgary/Calgary Lab Services (CLS), Calgary, AB, Canada
Background: Purine-rich box-1 (PU.1) is an ETS family hematopoiesis specific transcription factor essential for the development of multiple lineages of the immune system. Tightly regulated PU.1 expression at various stages is vital in establishing a sequential transcription network, driving B-cell development. Upstream regulatory elements are critical in orchestrating this dynamic PU.1 expression pattern and disruption of this control mechanism can lead to hematopoietic malignancy. The role of dysregulated PU.1 in mature B-cell lymphoma has been studied, however significance of PU.1 protein expression in Pre-B ALL remains unknown.
Design: Patients (Pts) were classified as Pre-B ALL utilizing morphology & flow cytometry data (WHO 2001). A tissue microarray (TMA) of BM biopsy samples (FFPE) was constructed using a standardized method. IHC staining was performed using PU.1 Ab (1:40, clone G148-74, Pharmingen, San Diego, CA) after heat-induced antigen retrieval, utilizing automated immunostainer (Dako). Nuclear staining intensity among neoplastic cells was scored on a 4 tier system. All pts received standardized chemotherapy +/-BMT. Clinical charts were reviewed for follow-up (FU) data. SPSS software was used for statistical analysis.
Results: A total of 81 pts (3-74 yrs; median 10 yrs; M:F 1.3:1) were included. 46/81 (57%) pts showed negative staining, while 28/81 (36%) revealed weak staining pattern. Only 6/81 (7%) had strong staining (2+ or >). After median FU of 36 months (range 7-90 months), 17 (21%) pts were deceased, while 64 (79%) were alive. Pts with strong PU.1 expression showed significantly shorter survival [p <0.005, Kaplan-Meier survival estimates, Log Rank Test (Figure1).
Conclusions: We report that dysregulated PU.1 protein expression, at levels that are usually seen in myeloid lineage, in Pre-B ALL pts is associated with aggressive clinical course. Expanded studies on a larger cohort are underway to establish this finding and the underlying mechanisms.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 166, Tuesday Afternoon