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.

The authors have declared no competing interest.

This research was funded by Ministerio de Ciencia e Innovacion (MCI), grant numbers RTI2018-094274-B-I00 to EC.; Fundacio La Marato de TV3 (projecte financat per Fundacio La Marato de TV3) 201920-30 to LH. Suport Grups de Recerca AGAUR 2014-SGR-795 and 2017-SGR-736 of the Generalitat de Catalunya to EC and JIM-S., respectively. AGAUR 2018 FIB00696, Generalitat de Catalunya to EMF-G. EC and JIM-S are Academia Researchers of the "Institucio Catalana de Recerca i Estudis Avancats" (ICREA) of the Generalitat de Catalunya.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of Hospital Clinic de Barcelona gave ethical approval for this work as FL samples were obtained from the Hematopathology collection of the Biobank of Hospital Clinic de Barcelona-IDIBAPS and CLL samples data and clinical annotations were obtained from the project of the Spanish ICGC consortium. The remaining data from other samples were obtained from GEO microarray public repository including previously published works with their particular ethical compliances stated in the original articles.

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