Transcriptomics

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Gene expression data of diagnostic childhood T-ALL samples and human thymocytes


ABSTRACT: Lymphotoxin-mediated activation of the lymphotoxin-β receptor (LTβR) has been implicated in several physiological and pathological processes, including lymphoid organ development, T-cell maturation, and solid and hematopoietic malignancies. Its role in T-cell acute lymphoblastic leukemia (T-ALL) or other T-cell malignancies has remained however to be investigated. Here we show that the genes encoding lymphotoxin (LT)-α and LTβ were expressed in T-ALL patient samples, more abundantly in the TAL/LMO molecular subtype, and in the TEL-JAK2 mouse model of cortical/mature T-ALL. Surface LTα1β2 protein was detected in primary mouse T-ALL cells, but only upon phorbol ester stimulation or absence of microenvironmental LTβR interaction. Indeed, in contrast to leukemic cells collected from transplanted Ltbr–/– mice or from co-cultures with Ltbr–/– mouse embryonic fibroblasts (MEF), those collected from Ltbr+/+ mice or from Ltbr+/+ MEF co-cultures presented no surface LT expression. Supporting the notion that LT signaling plays a role in T-ALL, inactivation of the Ltbr gene in mice resulted in a statistically significant delay in TEL-JAK2-induced leukemia onset. Expression of the Lta and Ltb genes was found to be increased at the early asymtptomatic stages of TEL-JAK2 T-ALL, when only low proportions of malignant thymocytes are present in normal sized thymus. Interestingly, young asymptomatic TEL-JAK2;Ltbr–/– mice presented significantly less leukemic thymocytes than TEL-JAK2;Ltbr+/+ mice. Together, these data indicate that early lymphotoxin expression by T-ALL cells activates LTβR signaling in thymic stromal cells, thus promoting leukemogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66638 | GEO | 2015/11/20

SECONDARY ACCESSION(S): PRJNA277531

REPOSITORIES: GEO

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