MicroRNA Expression Profiles in Pediatric Precursor T Lymphoblastic Leukemia/Lymphoma
M Czader, K Rizzo, G Vance, A Tewari, S Bhagavathi, J Olczyk, M Nassiri. Indiana University School of Medicine, Indianapolis, IN; University of Miami, Miami, FL
Background: Precursor T lymphoblastic leukemia/lymphoma (T-LL) represents 15% of newly diagnosed pediatric lymphoblastic leukemias/lymphomas. A significant proportion of cases present with high risk features such as bulky mediastinal mass, high WBC and CNS involvement. Despite improved outcomes due to therapy intensification, T-LL remains a high-risk disease with nearly 30% relapse rate. As further escalation of chemotherapy is not feasible, there is a need to optimize classification for improved treatment assignment and outcome prediction. To further study biological diversity of T-LL, we have investigated microRNA (miRNA) expression profiles in a series of T-LL patients. The role of miRNAs is related to targeting mRNAs encoding oncogenes and tumor suppressor genes. The association of miRNA profiles with clinicopathological variables and patient outcome has not been studied in T-LL.
Design: Thirty eight cases of T-LL were studied (bone marrows and lymph nodes). Median patient age was 9 years. There were 32 males. The median WBC at presentation was 23.3x109/L (range 2.5-945x109/L). The majority of patients had mediastinal mass and/or lymphadenopathy. Microarray studies were performed using Agilent human miRNA microarrays (version 2.0) containing 723 human and 76 human viral miRNAs cataloged in Sanger database v.10.1.
Results: Unsupervised hierarchical clustering showed two major T-LL subsets separated from normal bone marrow. These subsets were not defined by any studied clinicopathological parameters. Specifically, there was an overlap in miRNA profiles when cases were classified according to the NCI-Rome criteria into high- and low-risk age and WBC groups (age groups 0 to <1 year, 1-9 years, >10 years; WBC groups < and > 50x109/L). There was no difference in miRNA expression when patients were stratified according to gender. There were 41 miRNAs differentially expressed between T-LL samples from bone marrows vs. lymph nodes. Presence of cytogenetic abnormality was a major discriminative factor for miRNA expression with alterations of chromosome 11q23 associated with highest number of differentially expressed miRNAs.
Conclusions: Our study reports miRNA expression profiles in well defined series of pediatric T-LL. Different patterns of miRNA expression are seen at different sites of involvement and cytogenetic groups of this disease. Differentially expressed miRNAs define novel groups of this neoplasm, which may aid in subclassification and class prediction.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 224, Tuesday Morning