MARINA BOUSQUET

Involvement of long non-coding arns in
chemoresistance in acute myeloblastic leukemia

Our group is interested in the roles of long non-coding RNAs (lncRNAs) in normal and pathological hematopoiesis. lncRNAs are RNAs larger than 200 nucleotides without coding potential. Long considered as genomic “noise”, recent studies have shown that they are functional and may be involved in transcriptional control, epigenetic and post-transcriptional regulations. Although their involvement in tumorigenesis is being increasingly studied, little information has been reported regarding lncRNAs in acute myeloblastic leukemia (AML).

Through analyses of high-throughput sequencing data, we have been able to highlight specific expression profiles within AML patients and have identified two lncRNAs involved in mechanisms of chemotherapy resistance (De Clara, Haematologica, 2017; Gourvest, Leukemia, 2021).

Our goal is now to identify, using large-scale approaches (CRISPR screen, RNAseq analyses on large cohorts of AML patients), new lncRNAs involved in AML chemoresistance and to better understand their mechanisms of action by identifying their protein partners and nucleic targets.

The study of lncRNAs involved in chemoresistance could deepen our fundamental knowledge on the function of this class of RNAs still little known but also to identify new therapeutic targets and help the prognosis of AML.

Funding:

– ARC Foundation
– Regional League against Cancer
– FONROGA Foundation

10 main publications:

– Gourvest M, De Clara E, Wu HC, Touriol C, Meggetto F, de Thé H, Pyronnet S, Brousset P, Bousquet M (2021) A novel leukemic route of mutant NPM1 through nuclear import of the overexpressed long noncoding RNA LONA. Leukemia, Jun 15. doi: 10.1038/s41375-021-01307-0
– Gourvest M, Brousset P, Bousquet M (2019) Long Noncoding RNAs in Acute Myeloid Leukemia: Functional Characterization and Clinical Relevance. Cancers, 11,1638.
– De Clara E, Gourvest M, Ma H, Vergez F, Tosolini M, Dejean S, Demur C, Delabesse E, Recher C, Touriol C, Martelli MP, Falini B, Brousset P, Bousquet M (2017) Long non-coding RNA expression profile in cytogenetically normal acute myeloid leukemia identifies a distinct signature and a new biomarker in NPM1-mutated patients. Haematologica. 102(10):1718-1726
– Bousquet M, Noirot C, Accadbled F, Sales de Gauzy J, Castex MP, Brousset P, Gomez-Brouchet A. (2016) Whole exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations. Ann Oncol. 27(4):738-44
– Quelen C, Eloit Y, Noirot C, Bousquet M, Brousset P. (2016) RNA editing in acute myeloid leukaemia with normal karyotype. Br J Haematol. 173(5):788-90
– Berquet L, Valleron W, Grgurevic S, Quelen C, Zaki O, Quillet-Mary A, Davi F, Brousset P, Bousquet M*, Ysebaert L*. (2016) Small nucleolar RNA expression profiles refine the prognostic impact of IGHV mutational status on treatment-free survival in chronic lymphocytic leukaemia. Br J Haematol. 172(5):819-23
– Bousquet M, Zhuang G, Meng C, Ying W, Cheruku PS, Shie AT, Wang S, Ge G, Wong P, Wang G, Safe S, Zhou B. (2013) miR-150 blocks MLL-AF9-associated leukemia through oncogene repression. Mol Cancer Res. 11(8):912-22
– Bousquet M, Nguyen D, Chen C, Schields L, Lodish H (2012) miR-125b transforms myeloid cell lines by repressing multiple mRNA targets. Haematologica. 97(11):1713-21
– Bousquet M, Harris MH, Zhou B, Lodish H (2010) MicroRNA miR-125b causes leukemia. Proc Natl Acad Sci U S A 107(50):21558-63
– Bousquet M, Quelen C, Rosati R, Mansat-De Mas V , La Starza R, Bastard C, Lippert E, Talmant P, Lafage-Pochitaloff M, Leroux D, Gervais C, Viguié F, Lai JL, Terre C, Beverlo B, Sambani C, Hagemeijer A, Marynen P, Delsol G, Dastugue N, Mecucci C, Brousset P (2008) Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation. Journal of experimental medecine 205(11):2499-506