Project description:Cutaneous T-cell lymphomas (CTCL) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult due to a clinical and histological resemblance to benign inflammatory skin diseases. To address if microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we study miRNA expression in 199 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays we show that the most induced- (miR-326, miR-663b, miR-711) and repressed- (miR-203, miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Q-RT-PCR analysis of 104 patients with CTCL and benign skin disorders validates differential expression of 4 out of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A q-RT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity, sensitivity, and a classification accuracy of 95% indicating that miRNAs have a high diagnostic potential in CTCL.
Project description:Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing T cells. A subgroup of patients develops large cell transformation with progression to an aggressive lymphoma and with poor survival. We aimed to study the transformed CTCL (tCTCL) ecosystem using integrative approaches spanning whole-exome sequencing (WES), single-cell RNAseq, and immune profiling in a unique cohort of 56 patients with tCTCL
Project description:Transcriptional profiling controlled by PRKCQ of human CTCL cell lines MyLa and HuT 78 comparing cells transfected with non-targeting control with shPRKCQ cells at resting conditions and by TPA. The objective was to explore the role of PRKCQ in the pathogenesis of cutaneous T-cell lymphoma(CTCL).
Project description:Transcriptional profiling of human CTCL cell line H9 comparing cells transfected with vehicle control with ShBCL11B cells. Previous study have shown the involvements of BCL11b/BCL11B in T cell development and hematopoietic malignancies of T-cell origin. Objective was to explore the action of BCL11B in the pathogenesis of cutaneous T-cell lymphoma(CTCL).
Project description:Transcriptional profiling of human peripheral mononuclear cells in patients with leukemic cutaneous T-cell lymphoma (CTCL): a pilot study of effects of extracorporeal photopheresis (ECP) in clinically responsive and non-responsive/resistant patients
Project description:Cutaneous T-cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in the skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing 3 patient clusters. Of these, 2 clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB patients appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated with a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower-stage/treatment-responsive CTCL versus higher-stage/treatment-resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted. kuppe-00390 Assay Type: Gene Expression Provider: Affymetrix Array Designs: U133AAofAv2 Organism: Homo sapiens (ncbitax) Tissue Sites: Skin Material Types: total RNA, synthetic_RNA, organism_part, whole_organism Disease States: Cutaneous T-cell lymphoma
Project description:Cutaneous T-cell lymphomas form a heterogeneous group of non-Hodgkin lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. Here, we demonstrate by gene expression arrays that aurora kinase A is one of highly overexpressed genes of the serine/threonine kinase in CTCL. The finding was confirmed by qualitative RT-PCR, Western blotting and immunohistochemistry in CTCL cell lines and primary patient samples. Moreover, treatment with a specific aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest in G2 phase as well as apoptosis in CTCL cell lines. These new data provide a promising rationale for using aurora kinase A inhibition as a therapeutic modality of CTCL. 14 lesional skin biopsies of different MF patients (patch=3, plaque=6, tumor=4) and 9 healthy controls. Comparison between Cutaneus Tcell Lymphoma Samples and Healthy Control Tissue
Project description:Transcriptional profiling of human PCALCL cell line Mac1 comparing cells transfected with vehicle control with shEZH2 cells. Previous study have shown the involvements of EZH2 in T cell development and hematopoietic malignancies of T-cell origin. Objective was to explore the action of EZH2 in the pathogenesis of cutaneous T-cell lymphoma(CTCL).
Project description:Cutaneous T cell lymphoma (CTCL) can have clinical and histological features resembling benign inflammatory dermatosis (BID) and can be difficult to diagnose especially at the early stage of CTCL. We used microarrays to detail the global alteration of miRNA transcriptome and generate a diagnosis and prognosis signature.
Project description:Cutaneous T cell lymphoma (CTCL) can have clinical and histological features resembling benign inflammatory dermatosis (BID) and can be difficult to diagnose especially at the early stage of CTCL. We used microarrays to detail the global alteration of miRNA transcriptome and generate a diagnosis and prognosis signature.