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


METHODS
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.
Raetz
Elizabeth A
EA
Division of Pediatric Hematology-Oncology, Mount Sinai School of Medicine, New York, New York, USA. elizabeth.raetz@mssm.edu
Perkins
Sherrie L
SL
Bhojwani
Deepa
D
Smock
Kristi
K
Philip
Mary
M
Carroll
William L
WL
Min
Dong-Joon
DJ
D001853:Bone Marrow / Q000473:pathology; D002648:Child; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured