ArticleScience advances2015
Pim kinases modulate resistance to FLT3 tyrosine kinase inhibitors in FLT3-ITD acute myeloid leukemia.
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Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61citing papers in PubMed
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Who cites it
61 citing papers in PubMed, 91 citations in OpenAlex.
- Hematopoietic niche drives FLT3-ITD acute myeloid leukemia resistance to quizartinibHaematologica · 2019Trial
- Review
- TRIM22-mediated ubiquitin-dependent degradation of FLT3-ITD overcomes TKI resistance in acute myeloid leukemia.Life medicine · 2026Article
- Dual FLT3/PIM inhibitor dapolsertib in acute myeloid leukemia: results from the phase 1/2 DIAMOND-01 trial.Blood neoplasia · 2026Article
- The Dual PIM/FLT3 Inhibitor MEN1703 Combines Synergistically With Gilteritinib in FLT3-ITD-Mutant Acute Myeloid Leukaemia.Journal of cellular and molecular medicine · 2024Article
- In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy.Cancer cell · 2024Article
- Leukemic Stem Cells and Hematological Malignancies.International journal of molecular sciences · 2024Review
- Application of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia.Biomarker research · 2024Review
- Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation.Cancer research communications · 2024Article
- Very short insertions in the FLT3 gene are of therapeutic significance in acute myeloid leukemia.Blood advances · 2023Article
- Blockade of de novo pyrimidine biosynthesis triggers autophagic degradation of oncoprotein FLT3-ITD in acute myeloid leukemia.Oncogene · 2023Article
- Dual inhibition of CHK1/FLT3 enhances cytotoxicity and overcomes adaptive and acquired resistance in FLT3-ITD acute myeloid leukemia.Leukemia · 2023Article
- Transient TKI-resistant CD44+pBAD+ blasts undergo intrinsic homeostatic adaptation to promote the survival of acute myeloid leukemiaFrontiers in oncology · 2023Article
- Clinical Efficacies of FLT3 Inhibitors in Patients with Acute Myeloid Leukemia.International journal of molecular sciences · 2022Review
- Translatome proteomics identifies autophagy as a resistance mechanism to on-target FLT3 inhibitors in acute myeloid leukemia.Leukemia · 2022Article
- Synergistic antitumor activity of sorafenib and MG149 in hepatocellular carcinoma cells.BMB reports · 2022Article
- FLT3-targeted treatment for acute myeloid leukemia.International journal of hematology · 2022Review
- Mechanisms of resistance to targeted therapies for relapsed or refractory acute myeloid leukemia.Experimental hematology · 2022Review
- A review of FLT3 inhibitors in acute myeloid leukemia.Blood reviews · 2022Review
- Genetic ablation of Pim1 or pharmacologic inhibition with TP-3654 ameliorates myelofibrosis in murine models.Leukemia · 2022Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 2 institutions in 3 countries.
Alexa S GreenInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France. ; Department of Hematology, Charles Nicolle University Hospital, Rouen 76000, France.
Thiago T MacielINSERM UMR 1163, Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Paris 75015, France. ; Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris 75015, France. ; CNRS ERL 8254, Paris 75015, France. ; Laboratory of Excellence GR-Ex, Paris 75015 , France.
Marie-Anne HospitalInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Chae YinDivision of Hematology, Department of Medicine, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Fetta MazedInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Elizabeth C TownsendDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston 02115, MA 02115, USA.
Sylvain PilorgeInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France. ; INSERM U1065/C3M Team 2, Cell Death Differentiation Inflammation and Cancer, Nice 06204, France.
Mireille LambertInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Etienne PaubelleINSERM UMR 1163, Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Paris 75015, France. ; Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris 75015, France. ; CNRS ERL 8254, Paris 75015, France. ; Laboratory of Excellence GR-Ex, Paris 75015 , France.
Arnaud JacquelINSERM U1065/C3M Team 2, Cell Death Differentiation Inflammation and Cancer, Nice 06204, France.
Florence ZylbersztejnINSERM UMR 1163, Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Paris 75015, France. ; Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris 75015, France. ; CNRS ERL 8254, Paris 75015, France. ; Laboratory of Excellence GR-Ex, Paris 75015 , France.
Justine DecroocqINSERM UMR 1163, Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Paris 75015, France. ; Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris 75015, France. ; CNRS ERL 8254, Paris 75015, France. ; Laboratory of Excellence GR-Ex, Paris 75015 , France.
Laury PoulainInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Pierre SujobertInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Nathalie JacqueInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Kevin AdamInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Jason C C SoDivision of Hematology, Department of Medicine, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Olivier KosmiderInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Patrick AubergerINSERM U1065/C3M Team 2, Cell Death Differentiation Inflammation and Cancer, Nice 06204, France.
Olivier HermineINSERM UMR 1163, Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Paris 75015, France. ; Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris 75015, France. ; CNRS ERL 8254, Paris 75015, France. ; Laboratory of Excellence GR-Ex, Paris 75015 , France.
David M WeinstockDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston 02115, MA 02115, USA.
Catherine LacombeInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Patrick MayeuxInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Gary J VanasseNovartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Anskar Y LeungDivision of Hematology, Department of Medicine, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Ivan C MouraINSERM UMR 1163, Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Paris 75015, France. ; Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris 75015, France. ; CNRS ERL 8254, Paris 75015, France. ; Laboratory of Excellence GR-Ex, Paris 75015 , France.
Didier BouscaryInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Jerome TamburiniInstitut Cochin, Département Développement, Reproduction, Cancer, CNRS, UMR 8104, INSERM U1016, Paris 75014, France. ; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris 75005, France. ; Equipe Labellisée, Ligue Nationale Contre le Cancer (LNCC), Paris 75013, France.
Délégation Paris 5 · FRNovartis (United States) · US
Funding
Training Program in Molecular HematologyT32HL116324 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI NANCY BERLINER · 2013 to 2026
$7.4MNHLBI NIH HHS T32 HL116324
Abstract
Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is frequently detected in acute myeloid leukemia (AML) patients and is associated with a dismal long-term prognosis. FLT3 tyrosine kinase inhibitors provide short-term disease control, but relapse invariably occurs within months. Pim protein kinases are oncogenic FLT3-ITD targets expressed in AML cells. We show that increased Pim kinase expression is found in relapse samples from AML patients treated with FLT3 inhibitors. Ectopic Pim-2 expression induces resistance to FLT3 inhibition in both FLT3-ITD-induced myeloproliferative neoplasm and AML models in mice. Strikingly, we found that Pim kinases govern FLT3-ITD signaling and that their pharmacological or genetic inhibition restores cell sensitivity to FLT3 inhibitors. Finally, dual inhibition of FLT3 and Pim kinases eradicates FLT3-ITD(+) cells including primary AML cells. Concomitant Pim and FLT3 inhibition represents a promising new avenue for AML therapy.
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AMLFLT3Pimtyrosine kinase inhibitors
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