MALAT1Expression is Associated with Aggressive Behavior in Indolent B-Cell Neoplasms

Abstract

AbstractMALAT1is a long non-coding RNA with oncogenic roles in cancer but poorly studied in indolent B-cell neoplasms. Here,MALAT1expression was analyzed using RNA-seq, microarrays or qRT-PCR in primary samples from various clinico-biological subtypes of chronic lymphocytic leukemia (CLL, n=266) and follicular lymphoma (FL, n=61). In peripheral blood (PB) CLL samples, highMALAT1expression was associated with a significantly shorter time to treatment, independently from other known prognostic factors, such as IGHV mutational status. Coding genes whose expression levels were associated withMALAT1in CLL were predominantly related to oncogenic pathways stimulated in the lymph node (LN) microenvironment. Further analysis ofMALAT1expression by microarrays in paired CLL samples from PB/LN showed that its levels were maintained between both anatomical compartments, supporting that the clinical value ofMALAT1expression found in PB is mirroring expression differences already present in LN. Similarly, highMALAT1expression in FL predicted for a shorter progression-free survival, and its correlated expressed genes were associated with pathways promoting FL pathogenesis. In summary,MALAT1expression is related to pathophysiology and clinical behavior of indolent B-cell neoplasms. Particularly in CLL its levels could be a surrogate marker of the microenvironment stimulation and may contribute to refine the clinical management of these patients.