Table 1. The main studies dealing with gene expression profiling of peripheral T cell lymphomas.

Reference	Disease(s) explored	Comments
Tracey et al60	FM	The GEP of FM was investigated, and it showed concurrent deregulation of multiple genes involved in the tumour necrosis factor signalling pathway.
Martinez-Delgado et al14	PTCL/NOS	The authors found significant differences between the peripheral and lymphoblastic T cell lymphomas. The differences included a deregulation of the nuclear factor-κB signalling pathway.
Martinez-Delgado et al98	PTCL/NOS	The authors found two different subgroups of PTCL based on the expression of NF-κB related genes. One-third of PTCL clearly showed reduced expression of NF-κB genes, while the other group was characterised by high expression of these genes. Of interest, the expression profile associated with reduced expression of NF-κB genes was significantly associated with shorter survival of patients.
Ballester et al15	PTCL/NOS, AILT, ALCL	According to this study, PTCL/NOS could be divided into three molecular subgroups: U1, U2 and U3. The U1 gene expression signature included genes known to be associated with poor outcome in other tumours, such as CCND2. The U2 subgroup was associated with overexpression of genes involved in T cell activation and apoptosis, including NF-κB1 and BCL-2. The U3 subgroup was mainly defined by overexpression of genes involved in the IFN/JAK/STAT pathway. Notably, such distinction possibly reflected, at least in part, the presence of reactive components in the PTCL samples.
de Leval et al17	AILT	The molecular profile of AILT was characterised by a strong microenvironment and overexpression of several genes characteristic of normal follicular helper T (TFH) cells: CXCL13, BCL6, PDCD1, CD40L and NFATC1. Such a finding was reinforced by gene set enrichment analysis, which demonstrated that the AITL molecular signature was significantly enriched in TFH-specific genes.
Piccaluga et al20	PTCL/NOS	The authors showed that PTCL/NOS are most closely related to activated peripheral T lymphocytes, either CD4+ or CD8+, based on the GEP. In addition, PTCL/NOS displayed deregulation of relevant functional cell programmes. In particular, among others, PDGFRA, a gene encoding for a tyrosine kinase receptor, turned out to be aberrantly expressed by PTCL/NOS. Notably, phosphorylation of PDGFRA and sensitivity of cultured PTCL cells to imatinib were demonstrated.
Piccaluga et al21	PTCL/NOS	The authors found that CD52 is expressed in approximately 40% of PTCL/NOS at the same level as in normal T lymphocytes, being aberrantly downregulated in the remaining cases. Notably, they concluded that the estimation of CD52 expression may provide a rationale for the selection of patients with a higher probability of response to the anti-CD52 antibody alemtuzumab.
Piccaluga et al22	AILT	In this manuscript, the authors reported that AILT and other PTCL have rather similar GEP, possibly sharing common oncogenic pathways. In addition, they found that the molecular signature of follicular T helper cells was significantly overexpressed in AILT. Finally, several genes, such as PDGFRA and VEGF, which are deregulated in AILT and represent potential therapeutic targets, were identified.
Lamant et al16	ALCL	This was the first study to focus on ALCL. Unsupervised analysis classified ALCL in two clusters, corresponding essentially to morphological subgroups and clinical variables. Supervised analysis showed that ALK-positive ALCL and ALK-negative ALCL have different GEP, further confirming that they are different entities.
Cuadros et al18	PTCL/NOS	Five clusters of genes were identified, and their expression varied significantly among the samples. Genes in these clusters were functionally related to different cellular processes such as proliferation, inflammatory response, and T cell or B cell lineages. Notably, overexpression of genes in the proliferation signature was significantly associated with shorter survival of patients.

AILT, peripheral T cell lymphoma, angioimmunoblastic type; ALCL, anaplastic large cell lymphoma; ALK, anaplastic large cell lymphoma kinase; FM, mycosis fungoides; GEP, gene expression profile; PDGFRA, platelet-derived growth factor receptor α; PTCL/NOS, peripheral T cell lymphoma, not otherwise specified.