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Pediatr Blood Cancer. 2006 Aug;47(2):130-40.

Gene expression profiling reveals intrinsic differences between T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.

Author information

1
Division of Pediatric Hematology-Oncology, Mount Sinai School of Medicine, New York, New York, USA. elizabeth.raetz@mssm.edu

Abstract

BACKGROUND:

T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL) and are often thought to represent a spectrum of a single disease. The malignant cells in T-ALL and T-LL are morphologically indistinguishable, and they share the expression of common cell surface antigens and cytogenetic characteristics. However, despite these similarities, differences in the clinical behavior of T-ALL and T-LL are observed.

PROCEDURE:

We analyzed the gene expression profiles of T-ALL and T-LL samples obtained from Children's Oncology Group (COG) tumor banks using DNA arrays. Immunohistochemistry was also performed to validate the expression of selected targets.

RESULTS:

Unsupervised hierarchical clustering of all samples showed complete segregation of T-ALL and T-LL into distinct clusters. Next, we identified the top 201 genes that best differentiated T-ALL from T-LL using significance analysis of microarrays (SAM), a supervised statistical approach. Genes representing several functional groups were differentially expressed in T-LL and T-ALL. Prediction analysis of microarrays (PAM) identified a subset of genes, which accurately classified all 19 T-ALL and T-LL samples with an overall misclassification error rate of 0. Immunohistochemical validation of protein expression of selected genes identified by microarray analysis confirmed overexpression of MLL-1 in T-LL tumor cells compared to T-ALL and CD47 in T-ALL tumors cells when compared to T-LL.

CONCLUSIONS:

Despite significant similarities between the malignant T-cell precursors, clear differences in the gene expression profiles were observed between T-ALL and T-LL implying underlying differences in the biology of the two entities.

PMID:
16358311
DOI:
10.1002/pbc.20550
[Indexed for MEDLINE]

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