SF3B1 mutations provide genetic vulnerability to copper ionophores in human acute myeloid leukemia

Céline Moison, Deanne Gracias, Julie Schmitt, Simon Girard, Jean- François Spinella, Simon Fortier, Isabel Boivin, Rodrigo Mendoza- Sanchez, Bounkham Thavonekham, Tara MacRae, Nadine Mayotte, Eric Bonneil, Mark Wittman, James Carmichael, Réjean Ruel, Pierre Thibault, Josée Hébert, Anne Marinier, Guy Sauvageau.
SF3B1 mutations provide genetic vulnerability to copper ionophores in human acute myeloid leukemia.
Science Advances (2024).

KBTBD4-mediated Reduction of MYC Is Critical For Hematopoietic Stem Cell Expansion Upon UM171 Treatment

Jalila Chagraoui, Simon Girard, Laure Mallinger, Nadine Mayotte, Maria Florencia Tellechea, Guy Sauvageau
KBTBD4-mediated Reduction of MYC Is Critical For Hematopoietic Stem Cell Expansion Upon UM171 Treatment.
Blood (2023).

DELE1 haploinsufficiency causes resistance to mitochondrial stress-induced apoptosis in monosomy 5/del(5q) AML

Jean-François Spinella, Jalila Chagraoui, Céline Moison, Vincent P. Lavallée, Isabel Boivin, Deanne Gracias, Sylvie Lavallée, Guillaume Richard Carpentier , François Beliveau, Josée Hébert and Guy Sauvageau
DELE1 haploinsufficiency causes resistance to mitochondrial stress-induced apoptosis in monosomy 5/del(5q) AML.
Leukemia (2023).

Cohen et al. Blood Advances (2023)

Cohen S, Bambace N, Ahmad I, Roy J, Tang X, Zhang MJ, Burns LJ, Barabé F, Bernard L, Delisle JS, Kiss T, Lachance S, Roy DC, Veilleux O, Sauvageau G.
Improved Outcomes of UM171-Expanded Cord Blood Transplantation Compared with Other Graft Sources: Real-World Evidence.
Blood Advances (2023).

HMGA2

Moison C, Spinella JF, Chagraoui J, Lavallée VP, Lehnertz B, Thiollier C, Boivin I, Mayotte N, MacRae T, Marinier A, Hébert J, Sauvageau G.
HMGA2 expression defines a subset of AML with immature transcriptional signature and vulnerability to G2/M inhibition.
Blood Advances (2022).

CEACAM1 is a novel culture-compatible surface marker of expanded long-term reconstituting hematopoietic stem cells.

Ansari U, Tomellini E, Chagraoui J, Lehnertz B, Mayotte N, Bordeleau ME, Roux PP, Sauvageau G.
CEACAM1 is a novel culture-compatible surface marker of expanded long-term reconstituting hematopoietic stem cells.
Blood Advances (2022).

Krosl J, Bordeleau ME, Moison C, MacRae T, Boivin I, Mayotte N, Gracias D, Baccelli I, Lavallée VP, Bisaillon R, Lehnertz B, Mendoza-Sanchez R, Ruel R, Bertomeu T, Coulombe-Huntington J, Boucher G, Noronha N, Pabst C, Tyers M, Gendron P, Lemieux S, Barabé F, Marinier A, Hébert J, Sauvageau G.
Vesicular trafficking is a key determinant of the statin response in acute myeloid leukemia.
Blood Advances (2021).

HLF Expression Defines the Human Hematopoietic Stem Cell State.

Lehnertz B, Chagraoui J, MacRae T, Tomellini E, Corneau S, Mayotte N, Boivin I, Durand A, Gracias D, Sauvageau G.
HLF Expression Defines the Human Hematopoietic Stem Cell State.
Blood (2021).

Zinc finger protein E4F1 cooperates with PARP-1 and BRG1 to promote DNA double-strand break repair

Moison C, Chagraoui J, Caron MC, Gagné JP, Coulombe Y, Poirier GG, Masson JY, Sauvageau G.
Zinc finger protein E4F1 cooperates with PARP-1 and BRG1 to promote DNA double-strand break repair.
PNAS USA (2021).

UM171 Preserves Epigenetic Marks that Are Reduced in Ex Vivo Culture of Human HSCs via Potentiation of the CLR3-KBTBD4 Complex

Chagraoui J, Girard S, Spinella JF, Simon L, Bonneil E, Mayotte N, MacRae T, Coulombe-Huntington J, Bertomeu T, Moison C, Tomellini E, Thibault P, Tyers M, Marinier A, Sauvageau G.
UM171 Preserves Epigenetic Marks that Are Reduced in Ex Vivo Culture of Human HSCs via Potentiation of the CLR3-KBTBD4 Complex.
Cell Stem Cell (2021).

High frequency of germline RUNX1 mutations in patients with RUNX1-mutated AML

Simon L, Spinella JF, Yao CY, Lavallée VP, Boivin I, Boucher G, Audemard E, Bordeleau ME, Lemieux S, Hébert J, Sauvageau G.
High frequency of germline RUNX1 mutations in patients with RUNX1-mutated AML.
Blood (2020).

Genetic characterization of ABT-199 sensitivity in human AML.

Bisaillon R, Moison C, Thiollier C, Krosl J, Bordeleau ME, Lehnertz B, Lavallée VP, MacRae T, Mayotte N, Labelle C, Boucher G, Spinella JF, Boivin I, D’Angelo G, Lavallée S, Marinier A, Lemieux S, Hébert J, Sauvageau G.
Genetic characterization of ABT-199 sensitivity in human AML.
Leukemia (2020).

Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1-2 safety and feasibility study.

Cohen S, Roy J, Lachance S, Delisle JS, Marinier A, Busque L, Roy DC, Barabé F, Ahmad I, Bambace N, Bernard L, Kiss T, Bouchard P, Caudrelier P, Landais S, Larochelle F, Chagraoui J, Lehnertz B, Corneau S, Tomellini E, van Kampen JJA, Cornelissen JJ, Dumont-Lagacé M, Tanguay M, Li Q, Lemieux S, Zandstra PW, Sauvageau G.
Lancet Haematol (2019).

s a homeostatic inflammatory-detoxification response supporting human HSC self-renewal.

Chagraoui J, Lehnertz B, Girard S, Spinella JF, Fares I, Tomellini E, Mayotte N, Corneau S, MacRae T, Simon L, Sauvageau G.
UM171 induces a homeostatic inflammatory-detoxification response supporting human HSC self-renewal.
PLoS One (2019).

Mubritinib Targets the Electron Transport Chain Complex I and Reveals the Landscape of OXPHOS Dependency in Acute Myeloid Leukemia.

Baccelli I, Gareau Y, Lehnertz B, Gingras S, Spinella JF, Corneau S, Mayotte N, Girard S, Frechette M, Blouin-Chagnon V, Leveillé K, Boivin I, MacRae T, Krosl J, Thiollier C, Lavallée VP, Kanshin E, Bertomeu T, Coulombe-Huntington J, St-Denis C, Bordeleau ME, Boucher G, Roux PP, Lemieux S, Tyers M, Thibault P, Hébert J, Marinier A, Sauvageau G. Mubritinib Targets the Electron Transport Chain Complex I and Reveals the Landscape of OXPHOS Dependency in Acute Myeloid Leukemia.                                                                                                                                                         Cancer Cell (2019).

Complex karyotype AML displays G2/M signature and hypersensitivity to PLK1 inhibition.

Moison C, Lavallée VP, Thiollier C, Lehnertz B, Boivin I, Mayotte N, Gareau Y, Fréchette M, Blouin-Chagnon V, Corneau S, Lavallée S, Lemieux S, Marinier A, Hébert J, Sauvageau G.
Complex karyotype AML displays G2/M signature and hypersensitivity to PLK1 inhibition.
Blood Advances (2019).

Integrin-α3 Is a Functional Marker of Ex Vivo Expanded Human Long-Term Hematopoietic Stem Cells.

Tomellini E, Fares I, Lehnertz B, Chagraoui J, Mayotte N, MacRae T, Bordeleau MÈ, Corneau S, Bisaillon R, Sauvageau G.
Integrin-α3 Is a Functional Marker of Ex Vivo Expanded Human Long-Term Hematopoietic Stem Cells.
Cell Reports (2019).

Transcriptomic landscape of acute promyelocytic leukemia reveals aberrant surface expression of the platelet aggregation agonist Podoplanin.

Lavallée VP, Chagraoui J, MacRae T, Marquis M, Bonnefoy A, Krosl J, Lemieux S, Marinier A, Pabst C, Rivard GÉ, Hébert J, Sauvageau G.
Transcriptomic landscape of acute promyelocytic leukemia reveals aberrant surface expression of the platelet aggregation agonist Podoplanin.
Leukemia (2018).

Chemogenomic Landscape of RUNX1-mutated AML Reveals Importance of RUNX1 Allele Dosage in Genetics and Glucocorticoid Sensitivity.

Simon L, Lavallée VP, Bordeleau ME, Krosl J, Baccelli I, Boucher G, Lehnertz B, Chagraoui J, MacRae T, Ruel R, Chantigny Y, Lemieux S, Marinier A, Hébert J, Sauvageau G.
Chemogenomic Landscape of RUNX1-mutated AML Reveals Importance of RUNX1 Allele Dosage in Genetics and Glucocorticoid Sensitivity.
Clinical cancer research (2017).

H3K27M/I mutations promote context-dependent transformation in acute myeloid leukemia with RUNX1 alterations.

Lehnertz B, Zhang YW, Boivin I, Mayotte N, Tomellini E, Chagraoui J, Lavallée VP, Hébert J, Sauvageau G.
H3K27M/I mutations promote context-dependent transformation in acute myeloid leukemia with RUNX1 alterations.
Blood (2017).

EPCR expression marks UM171-expanded CD34+ cord blood stem cells. Blood.

Fares I, Chagraoui J, Lehnertz B, MacRae T, Mayotte N, Tomellini E, Aubert L, Roux PP, Sauvageau G.
EPCR expression marks UM171-expanded CD34+ cord blood stem cells. 
Blood (2017).

A novel approach for the identification of efficient combination therapies in primary human acute myeloid leukemia specimens. Blood Cancer J.

Baccelli I, Krosl J, Boucher G, Boivin I, Lavallée V-P, Hébert J, Lemieux S, Marinier A, Sauvageau G.
A novel approach for the identification of efficient combination therapies in primary human acute myeloid leukemia specimens.
Blood Cancer Journal (2017).

GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo. Blood.

Pabst C, Bergeron A, Lavallée VP, Yeh J, Gendron P, Norddahl GL, Krosl J, Boivin I, Deneault E, Simard J, Imren S, Boucher G, Eppert K, Herold T, Bohlander SK, Humphries K, Lemieux S, Hébert J, Sauvageau G, Barabé F.
GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.
Blood (2016).

The transcriptomic landscape and directed chemical interrogation of MLL-rearranged acute myeloid leukemias

Lavallée VP, Baccelli I, Krosl J, Wilhelm B, Barabé F, Gendron P, Boucher G, Lemieux S, Marinier A, Meloche S, Hébert J, Sauvageau G.
The transcriptomic landscape and directed chemical interrogation of MLL-rearranged acute myeloid leukemias.
Nature Genetics (2015).

E4F1 is a master regulator of CHK1-mediated functions.

Grote D, Moison C, Duhamel S, Chagraoui J, Girard S, Yang J, Mayotte N, Coulombe Y, Masson JY, Brown GW, Meloche S, Sauvageau G.
E4F1 is a master regulator of CHK1-mediated functions.
Cell Reports (2015).

Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate.

Fortier S, MacRae T, Bilodeau M, Sargeant T, Sauvageau G.
Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate.
PNAS USA (2015).

Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal.

Fares I, Chagraoui J, Gareau Y, Gingras S, Ruel R, Mayotte N, Csaszar E, Knapp DJ, Miller P, Ngom M, Imren S, Roy DC, Watts KL, Kiem HP, Herrington R, Iscove NN, Humphries RK, Eaves CJ, Cohen S, Marinier A, Zandstra PW, Sauvageau G.
Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal.
Science (2014).

UBAP2L is a novel BMI1-interacting protein essential for hematopoietic stem cell activity.

Bordeleau ME, Aucagne R, Chagraoui J, Girard S, Mayotte N, Bonneil E, Thibault P, Pabst C, Bergeron A, Barabé F, Hébert J, Sauvageau M, Boutonnet C, Meloche S, Sauvageau G.
UBAP2L is a novel BMI1-interacting protein essential for hematopoietic stem cell activity.
Blood (2014).

Identification of small molecules that support human leukemia stem cell activity ex vivo.

Pabst C, Krosl J, Fares I, Boucher G, Ruel R, Marinier A, Lemieux S, Hébert J, Sauvageau G.
Identification of small molecules that support human leukemia stem cell activity ex vivo.
Nature Methods (2014).

C-terminal domain of MEIS1 converts PKNOX1 (PREP1) into a HOXA9-collaborating oncoprotein.

Bisaillon R, Wilhelm BT, Krosl J, Sauvageau G.
C-terminal domain of MEIS1 converts PKNOX1 (PREP1) into a HOXA9-collaborating oncoprotein.
Blood (2011).

An anticlastogenic function for the Polycomb Group gene Bmi1.

Chagraoui J, Hébert J, Girard S, Sauvageau G.
An anticlastogenic function for the Polycomb Group gene Bmi1.
PNAS USA (2011).

Genome-wide interrogation of Mammalian stem cell fate determinants by nested chromosome deletions.

Fortier S, Bilodeau M, Macrae T, Laverdure JP, Azcoitia V, Girard S, Chagraoui J, Ringuette N, Hébert J, Krosl J, Mayotte N, Sauvageau G.
Genome-wide interrogation of Mammalian stem cell fate determinants by nested chromosome deletions.
PLoS Genetics (2010).

Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer.

Sauvageau M, Sauvageau G.
Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer.
Cell Stem Cell (2010).

An RNAi screen identifies Msi2 and Prox1 as having opposite roles in the regulation of hematopoietic stem cell activity.

Hope KJ, Cellot S, Ting SB, MacRae T, Mayotte N, Iscove NN, Sauvageau G.
An RNAi screen identifies Msi2 and Prox1 as having opposite roles in the regulation of hematopoietic stem cell activity.
Cell Stem Cell (2010).

A functional screen to identify novel effectors of hematopoietic stem cell activity.

Deneault E, Cellot S, Faubert A, Laverdure JP, Fréchette M, Chagraoui J, Mayotte N, Sauvageau M, Ting SB, Sauvageau G.
A functional screen to identify novel effectors of hematopoietic stem cell activity.
Cell (2009).

Quantitative expression profiling guided by common retroviral insertion sites reveals novel and cell type specific cancer genes in leukemia.

Sauvageau M, Miller M, Lemieux S, Lessard J, Hébert J, Sauvageau G.
Quantitative expression profiling guided by common retroviral insertion sites reveals novel and cell type specific cancer genes in leukemia.
Blood (2008).

Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.

Lessard J, Sauvageau G.
Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.
Nature (2003).

HOXB4-induced expansion of adult hematopoietic stem cells ex vivo.

Antonchuk J, Sauvageau G, Humphries RK.
HOXB4-induced expansion of adult hematopoietic stem cells ex vivo.
Cell (2002).

Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b.

Kroon E, Krosl J, Thorsteinsdottir U, Baban S, Buchberg AM, Sauvageau G.
Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b.
EMBO Journal (1998).