The Gene Expression Profile of T-Cell Prolymphocytic Leukemia with inv(14)(q11q32) Reflects the Pattern of Chromosomal Imbalances.

T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoma derived from mature T-cells, which is in most cases characterized by the presence of an inv(14)(q11q32) and a characteristic pattern of secondary chromosomal aberrations. DNA microarray technology was employed to compare the transcriptomes of eight immunomagnetically purified CD3+ normal donor derived peripheral blood cells with five highly purified inv(14)-positive T-PLL blood samples. In comparison between the two experimental groups 740 genes were identified as differentially expressed including functionally important genes involved in lymphomagenesis, cell cycle regulation, apoptosis and DNA repair. Notably, the differentially expressed genes were found to be significantly enriched in genomic regions affected by recurrent chromosomal imbalances. Up-regulated genes clustered significantly on chromosome arms 6p and 8q and down-regulated genes on 6q, 8p, 10p, 11q and 18p. High-resolution copy-number determination using SNP-chip technology in twelve inv(14)/t(14;14)-positive T-PLL including those analyzed for gene expression refined chromosomal breakpoints as well as regions of imbalances. In conclusion, combined transcriptional and molecular cytogenetic profiling identified novel specific chromosomal loci and genes which are likely to be involved in disease progression and suggests a gene dosage effect as a pathogenic mechanism in T-PLL.