CD9 in acute myeloid leukemia: Prognostic role and usefulness to target leukemic stem cells

Touzet, Lucas; Dumézy, Florent; Roumier, Christophe; Berthon, Céline; Bories, Claire; Quesnel, Bruno; Preudhomme, Claude; Boyer, Thomas D.

doi:10.1002/cam4.2007

Cited by 26 publications

(30 citation statements)

References 30 publications

(34 reference statements)

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“…As a member of the tetraspanin superfamily, CD9 was rst identi ed by Kersey et al as the human lymphohematopoietic progenitor cell surface antigen p24 using a monoclonal antibody that bound to acute lymphoblastic leukemia cells [47]. CD9 has been reported to be expressed in 40% of human AML samples and associated with clinical outcomes in AML [21]. In this study, we demonstrate that CD9 is highly expressed in the CD34 + CD38 − AML LSCs, and extremely low or no expression in normal HSCs, which could serve as a hopeful therapeutic target in AML.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it was reported that CD9 plays an important role in cell adhesion, movement, differentiation, proliferation, apoptosis and resistance [15][16][17][18][19]. Although CD9 has been reported to identify cancer stem cells in several types of cancers including pancreatic cancer, glioblastoma and B-acute lymphoblastic leukemia, and is related to the prognosis of AML, biological characteristic and regulatory mechanism of CD9 + AML LSCs remain elucidated [15,[20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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CD9 Defines Acute Myeloid Leukemia Stem Cells and is Regulated by Alpha-2-Macroglobulin

Liu¹,

Wang²,

Zhang³

et al. 2020

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Background: Leukemia stem cells (LSCs) are responsible for the initiation, progress and relapse of acute myeloid leukemia (AML). Therefore, the therapy strategy of targeting LSCs is hopeful to eradicate AML. In this study, we aim to identify LSC-specific surface markers and uncover the underlying mechanism of AML LSCs.Methods: Microarray gene expression data were used to investigate the candidate AML-LSC specific markers. CD9 expression was evaluated by flow cytometry in AML cell lines, patients with AML and normal donors. The biological characteristics of CD9-positive (CD9+) cells were analyzed by in vitro proliferation, chemotherapeutic drug resistance, migration and in vivo xenotransplantation assays. The molecular mechanism involved in CD9+ cell function was investigated by gene expression profiling. Effect of alpha-2-macroglobulin (A2M) on CD9+ cells was analyzed by proliferation, drug resistance and migration assays.Results: CD9 as a cell surface protein was specifically expressed on AML LSCs, but almost not expressed on normal hematopoietic stem cells (HSCs). CD9+ cells exhibited more resistance to chemotherapy drugs and higher migration potential than CD9-negative (CD9-) cells. More importantly, CD9+ cells possess the ability to reconstitute human AML in immunocompromised mice and promote tumor growth, suggesting CD9+ cells define the LSC population. Furthermore, we identified A2M plays a crucial role in CD9+ LSCs stemness maintenance. Down-regulation of A2M impairs drug-resistance and migration of CD9+ cells.Conclusion: Our findings suggest that CD9 is a new biomarker of AML LSCs and may serve as a promising therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD9 Defines Acute Myeloid Leukemia Stem Cells and is Regulated by Alpha-2-Macroglobulin

Liu¹,

Wang²,

Zhang³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, it was reported that CD9 plays an important role in cell adhesion, movement, differentiation, proliferation, apoptosis and resistance to chemotherapy [15][16][17][18][19]. Although CD9 has been reported to identify cancer stem cells in several types of cancers including pancreatic cancer, glioblastoma and B-acute lymphoblastic leukemia, and is related to the prognosis of AML [15,[20][21][22]. However, biological characteristic and regulatory mechanism of CD9 + AML LSCs remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

CD9 is a leukemic stem cell-specific marker in human acute myeloid leukemia

Liu¹,

Wang²,

Zhang³

et al. 2020

Preprint

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Background: Leukemia stem cells (LSCs) are responsible for the initiation, progressing and relapse of acute myeloid leukemia (AML). Therefore, the therapy strategy of targeting LSCs is hopeful to eradicate AML. In this study, we aimed to identify LSCs-specific surface markers and uncover the underlying mechanism of AML LSCs.Methods: Microarray gene expression data were used to investigate the candidate AML-LSCs specific markers. CD9 expression was evaluated by flow cytometry (FC) in AML cell lines, patients with AML and normal donors. The biological characteristics of CD9-positive (CD9+) cells were analyzed by in vitro proliferation, chemotherapeutic drug resistance, migration and in vivo xenotransplantation assays. The molecular mechanism involved in CD9+ cell function was investigated by gene expression profiling. Effects of alpha-2-macroglobulin (A2M) on CD9+ cells were analyzed in the aspects of proliferation, drug resistance and migration.Results：CD9, as a cell surface protein, is specifically expressed on AML LSCs, but barely can be detected on normal hematopoietic stem cells (HSCs). CD9+ cells exhibits more resistance to chemotherapy drugs and higher migration potential than CD9-negative (CD9-) cells. More importantly, CD9+ cells possess the ability to reconstitute human AML in immunocompromised mice and promote leukemia growth, suggesting CD9+ cells define the LSCs population. Furthermore, we identified A2M as an important role in CD9+ LSCs stemness maintenance. Knock down of A2M impairs drug-resistance and migration of CD9+ cells.Conclusion: Our findings suggested that CD9 is a new biomarker of AML LSCs and may serve as a promising therapeutic target.

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“…Cancer drug resistance is a complex phenomenon influenced by drug inactivation, drug target alteration, drug efflux, DNA damage, cell heterogeneity, epigenetic and methylation effects, impairment in cellular communication or any combination of these mechanisms [1]. Development of therapeutic resistance is a persistent problem and is a major cause of cancer deaths worldwide [2].…”

mentioning

confidence: 99%

“…Development of therapeutic resistance is a persistent problem and is a major cause of cancer deaths worldwide [2]. Cancer cells may acquire resistance to chemotherapy, or may have a high level of resistance through a variety of mechanisms [1]. One example of this is observed in the tumor microenvironment where stem cells can play a crucial role in chemotherapeutic resistance [2].…”

mentioning

confidence: 99%