P. Brousset / F. Meggetto

  RNA biology in hematological cancers

 

 

 

 

 

 

Our research project at a glance

 

Non coding RNA (ncRNA) are RNA without protein-coding potential.  Despite intensive research on ncRNA, our overall knowledge of ncRNA function in carcinogenesis remains very limited. One of the main challenges of our team in understanding the function of a specific non-coding RNA such as long and micro ncRNA in cancer, is deciphering their interactome (other RNAs, specific protein complexes, regions of DNA…), and regulations.

 

Objectives

 

In the last decade, it has become increasingly clear that post-transcriptional control of gene expression plays an essential role in tumor cell dysregulation. Studies at the RNA level have been focused for a long time on mRNA, the best known RNA family that represents only a small part of transcripts (2 to 5% of total RNAs). However, the human genome contains much more than just protein-coding genes and the majority of transcribed RNAs are non-coding (ncRNA) such as microRNAs (miRNA), long non-coding RNAs (lncRNA), interfering RNAs, piwiRNAs, or small nucleolar RNAs (snoRNA). Evidence is accumulating that these ncRNAs play key roles in regulating numerous pathways involved in cancer development and progression.

The lab explores the expression profiles and functions of microRNAs and lncRNAs in hematological malignancies, their interaction with proteins and their protein coding potential (with a focus on primary miRNA transcripts, pri-miR). Two types of tumors for which our team has an international expertise or represent cancers with potential of resistance are investigated: T-cell lymphoma including anaplastic large cell lymphoma and acute myeloid leukemia.

Our objectives are:

  • to decipher how ncRNAs dysregulation in leukemias/lymphomas could impact on their prognosis (relapse, response and resistance to treatment) and ideally to identify prognostic biomarkers.
  • to investigate the role of ER stress on ncRNAs expression in leukemia and their impact on tumor progression and response to treatment.
  • to study the physiological and pathological role of these ncRNA including the identification of their downstream target genes, whose role in classical (proliferation, survival, invasion) pathways of cancerogenesis will be functionally characterized.
  • to study the upstream mechanisms of ncRNA regulation (epigenetic control of their expression, control of their expression by microRNA encoded peptites (miPEPs), control of their stability by specific endoribonucleases).

 

Key words

 

  • miRNA
  • lncRNA
  • Acute myeloid leukemia
  • Anaplastic large cell lymphoma
  • ALK
  • Target therapy
  • ER stress
  • Resistance

 

Selected publications


2017

De Clara, E; Gourvest, M; Ma, H; Vergez, F; Tosolini, M; Dejean, S; Demur, C; Delabesse, E; Recher, C; Touriol, C; Martelli, M P; Falini, B; Brousset, P; Bousquet, M

Long non-coding RNA expression profile in cytogenetically normal acute myeloid leukemia identifies a distinct signature and a new biomarker in NPM1-mutated patients Journal Article

Haematologica, 102 (10), pp. 1718-1726, 2017, ISSN: 1592-8721 (Electronic) 0390-6078 (Linking).

Links | BibTeX

Laurent, C; Baron, M; Amara, N; Haioun, C; Dandoit, M; Maynadie, M; Parrens, M; Vergier, B; Copie-Bergman, C; Fabiani, B; Traverse-Glehen, A; Brousse, N; Copin, M C; Tas, P; Petrella, T; Rousselet, M C; Briere, J; Charlotte, F; Chassagne-Clement, C; Rousset, T; Xerri, L; Moreau, A; Martin, A; Damotte, D; Dartigues, P; Soubeyran, I; Peoch, M; Dechelotte, P; Michiels, J F; de Mascarel, A; Berger, F; Bossard, C; Arbion, F; Quintin-Roue, I; Picquenot, J M; Patey, M; Fabre, B; Sevestre, H; Le Naoures, C; Chenard-Neu, M P; Bastien, C; Thiebault, S; Martin, L; Delage, M; Filleron, T; Salles, G; Molina, T J; Delsol, G; Brousset, P; Gaulard, P

Impact of Expert Pathologic Review of Lymphoma Diagnosis: Study of Patients From the French Lymphopath Network Journal Article

J Clin Oncol, 35 (18), pp. 2008-2017, 2017, ISSN: 1527-7755 (Electronic) 0732-183X (Linking).

Links | BibTeX

2015

Hoareau-Aveilla, C; Valentin, T; Daugrois, C; Quelen, C; Mitou, G; Quentin, S; Jia, J; Spicuglia, S; Ferrier, P; Ceccon, M; Giuriato, S; Gambacorti-Passerini, C; Brousset, P; Lamant, L; Meggetto, F

Reversal of microRNA-150 silencing disadvantages crizotinib-resistant NPM-ALK(+) cell growth Journal Article

J Clin Invest, 125 (9), pp. 3505-18, 2015, ISSN: 1558-8238 (Electronic) 0021-9738 (Linking).

Links | BibTeX

2012

Dejean, E; Foisseau, M; Lagarrigue, F; Lamant, L; Prade, N; Marfak, A; Delsol, G; Giuriato, S; Gaits-Iacovoni, F; Meggetto, F

ALK+ALCLs induce cutaneous, HMGB-1-dependent IL-8/CXCL8 production by keratinocytes through NF-kappaB activation Journal Article

Blood, 119 (20), pp. 4698-707, 2012, ISSN: 1528-0020 (Electronic) 0006-4971 (Linking).

Links | BibTeX

2011

Bergalet, J; Fawal, M; Lopez, C; Desjobert, C; Lamant, L; Delsol, G; Morello, D; Espinos, E

HuR-mediated control of C/EBPbeta mRNA stability and translation in ALK-positive anaplastic large cell lymphomas Journal Article

Mol Cancer Res, 9 (4), pp. 485-96, 2011, ISSN: 1557-3125 (Electronic) 1541-7786 (Linking).

Links | BibTeX

Dejean, E; Renalier, M H; Foisseau, M; Agirre, X; Joseph, N; de Paiva, G R; Al Saati, T; Soulier, J; Desjobert, C; Lamant, L; Prosper, F; Felsher, D W; Cavaille, J; Prats, H; Delsol, G; Giuriato, S; Meggetto, F

Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas Journal Article

Leukemia, 25 (12), pp. 1882-90, 2011, ISSN: 1476-5551 (Electronic) 0887-6924 (Linking).

Links | BibTeX

Desjobert, C; Renalier, M H; Bergalet, J; Dejean, E; Joseph, N; Kruczynski, A; Soulier, J; Espinos, E; Meggetto, F; Cavaille, J; Delsol, G; Lamant, L

MiR-29a down-regulation in ALK-positive anaplastic large cell lymphomas contributes to apoptosis blockade through MCL-1 overexpression Journal Article

Blood, 117 (24), pp. 6627-37, 2011, ISSN: 1528-0020 (Electronic) 0006-4971 (Linking).

Links | BibTeX

Lamant, L; McCarthy, K; d'Amore , E; Klapper, W; Nakagawa, A; Fraga, M; Maldyk, J; Simonitsch-Klupp, I; Oschlies, I; Delsol, G; Mauguen, A; Brugieres, L; Le Deley, M C

Prognostic impact of morphologic and phenotypic features of childhood ALK-positive anaplastic large-cell lymphoma: results of the ALCL99 study Journal Article

J Clin Oncol, 29 (35), pp. 4669-76, 2011, ISSN: 1527-7755 (Electronic) 0732-183X (Linking).

Links | BibTeX

2010

Giuriato, S; Foisseau, M; Dejean, E; Felsher, D W; Al Saati, T; Demur, C; Ragab, A; Kruczynski, A; Schiff, C; Delsol, G; Meggetto, F

Conditional TPM3-ALK and NPM-ALK transgenic mice develop reversible ALK-positive early B-cell lymphoma/leukemia Journal Article

Blood, 115 (20), pp. 4061-70, 2010, ISSN: 1528-0020 (Electronic) 0006-4971 (Linking).

Links | BibTeX

2008

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; Viguie, F; Lai, J L; Terre, C; Beverlo, B; Sambani, C; Hagemeijer, A; Marynen, P; Delsol, G; Dastugue, N; Mecucci, C; Brousset, P

Myeloid cell differentiation arrest by miR-125b-1 in myelodysplastic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation Journal Article

J Exp Med, 205 (11), pp. 2499-506, 2008, ISSN: 1540-9538 (Electronic) 0022-1007 (Linking).

Links | BibTeX