Genomic and Transcriptomic Analyses Revealed Differences and Similarities Between T-Lbl and T-ALL .

T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) share common morphologic and immunophenotypic features and are treated with similar therapeutic approaches. Nonetheless, they show distinct clinical presentations suggesting that they may represent two different biological entities. In order to gain insights into the biological characteristics of these T-cell malignancies we applied genomic and transcriptomic approaches on residual diagnostic specimens from pediatric patients affected by T-ALL or T-LBL.

Genome-wide gene expression profiling (HG-U133Plus2.0, Affymetrix) was performed for 20 patients affected by T-LBL and 10 patients affected by T-ALL. In order to control for normal cells contamination present in the nodal biopsies (T-LBL) and bone marrow aspirates (T-ALL), we used gene expression profiles of B-cell lymphoblastic lymphoma and common (CD10+) lymphoblastic leukemia, respectively.

Genes differentially expressed in nodal versus bone marrow-derived samples were subtracted from the T-LBL versus T-ALL signature allowing the identification of a subset of genes able to discriminate the two T-cell malignancies regardless of their localization. This gene signature includes genes involved in chemotactic response, cell adhesion and angiogenesis which may play a role in the different tumor cell localization. Indeed, genes involved in promoting angiogenesis, invasion and nodal localization were up-regulated in T-LBL. Copy number analysis was performed using single nucleotide polymorphism (SNP) arrays (Human Mapping 100K arrays, Affymetrix) on a subset of the samples (9 T-ALL and 9 T-LBL) analyzed by gene expression profiling. This analysis detected approximately 200 genetic loci recurrently affected by copy number alterations in T-ALL and/or T-LBL. The most common aberration was the 9p21.3 deletion which includes CDKN2A/B. Consistent with previous reports amplifications involving MYB were identified in two cases of T-ALL. Although most aberrations were commonly found in both entities several were recurrently detected in T-LBL but not in T-ALL and vice versa.

Taken together these results suggest that T-LBL and T-ALL share a large fraction of their biological features; nevertheless each malignancy displays also a unique pattern of genetic lesions and specific gene expression signatures, which may contribute to the understanding of the distinct evolution of these T-cell malignancies.

No relevant conflicts of interest to declare.