MALAT1 Expression is Associated with Aggressive Behavior in Indolent B-Cell Neoplasms

MALAT1 is a long non-coding RNA with oncogenic roles in cancer but poorly studied in indolent B-cell neoplasms. Here, MALAT1 expression 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, high MALAT1 expression 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 with MALAT1 in CLL were predominantly related to oncogenic pathways stimulated in the lymph node (LN) microenvironment. Further analysis of MALAT1 expression by microarrays in paired CLL samples from PB/LN showed that its levels were maintained between both anatomical compartments, supporting that the clinical value of MALAT1 expression found in PB is mirroring expression differences already present in LN. Similarly, high MALAT1 expression in FL predicted for a shorter progression-free survival, and its correlated expressed genes were associated with pathways promoting FL pathogenesis. In summary, MALAT1 expression 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.