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Molecular signatures for Hairy cell leukemia

ABSTRACT: Analysis of the expression profile of 298 mRNA's, measured with the nCounter (Nanostring Technologies platform), in 13 samples from the peripheral blood of Hairy cell leukemia patients Hairy cell leukemia (HCL) is a rare chronic B-cell malignancy, characterized by infiltration of bone marrow, blood and spleen by typical “hairy cells” that bear the BRAFV600E mutation. However, in addition to the intrinsic activation of the MAP kinase pathway as a consequence of the BRAFV600E mutation, the potential participation of other signaling pathways to the pathophysiology of the disease remains unclear. Using mRNA gene expression profiling based on the Nanostring technology and the analysis of 290 genes with crucial roles in B-cell lymphomas, we defined a 17 gene expression signature specific for HCL. Our analysis revealed intrinsic activation of the non-canonical NF-B pathway with underexpression of BIRC2 and BIRC3, two specific non-canonical NF-B inhibitors. Western blots confirmed activation of this pathway with increased processing of p100 in primary HCL samples. Separate analysis of samples from classical and variant forms of hairy cell leukemia showed almost similar mRNA expression profiles apart from overexpression in vHCL of the immune checkpoints CD274 and PDCD1LG2 and underexpression of FAS. Our results provide a better understanding of the pathogenesis of HCL and describe new and potential targets for treatment approaches and guidance for studies in the molecular mechanisms of HCL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161279 | GEO | 2020/11/12

REPOSITORIES: GEO

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