BCL-2 inhibition with ABT-737 prolongs survival in an NRAS/BCL-2 mouse model of AML by targeting primitive LSK and progenitor cells

Author:

Beurlet Stephanie12,Omidvar Nader3,Gorombei Petra12,Krief Patricia12,Le Pogam Carole12,Setterblad Niclas2,de la Grange Pierre4,Leboeuf Christophe256,Janin Anne256,Noguera Maria-Elena6,Hervatin Florence7,Sarda-Mantel Laure28,Konopleva Marina9,Andreeff Michael9,Tu Andrea W.10,Fan Alice C.11,Felsher Dean W.11,Whetton Anthony12,Pla Marika12,West Robert13,Fenaux Pierre126,Chomienne Christine126,Padua Rose Ann126

Affiliation:

1. Institut National de la Santé et de la Recherche Médicale U940, Paris, France;

2. Université Paris-Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Unité Mixe de Recherche de Santé 940, Unité Mixe de Recherche de Santé 728, Paris, France;

3. Haematology Department, Cardiff University School of Medicine, Cardiff, United Kingdom;

4. GenoSplice Technology, Institut Universitaire d'Hématologie, Paris, France;

5. Institut National de la Santé et de la Recherche Médicale U728, Paris, France;

6. Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France;

7. Commissariat à l'Energie Atomique, Service Hospitalier Frédéric Joliot, Orsay, France;

8. Institut National de la Santé et de la Recherche Médicale U773, Université Paris-Diderot, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris Hôpital Bichat, Paris, France;

9. The University of Texas, MD Anderson Cancer Center, Houston, TX;

10. ProteinSimple, Santa Clara, CA;

11. Stanford University Cancer Center, Stanford, CA;

12. School of Cancer and Enabling Science, University of Manchester, Manchester, United Kingdom; and

13. Public Health, Cardiff University School of Medicine, Cardiff, United Kingdom

Abstract

Key Points BCL-2 homology domain 3 mimetic inhibitor ABT-737 targets leukemia initiating cells and progenitors. Dephosphorylates RAS signaling proteins and regulates proliferation and differentiation genes detected by gene expression profiling.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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