CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

Liu, Yongliang; Wang, Guiqin; Zhang, Jiasi; Chen, Xue; Xu, Huailong; Heng, Gang; Zhao, Yuemin; Li, Jiatao; Ni, Yuanli; Zhang, Yingzi; Shan, Juanjuan; Qian, Cheng

doi:10.21203/rs.3.rs-55355/v3

Cited by 2 publications

(2 citation statements)

References 41 publications

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“…When comparing ABX Placebo over H 2 O Placebo, multiple genes were signi cantly enriched including PAX2, PAX8, WNT7a, CALB1, A2ML, IHH and PLEKHS1, among others that play key roles in cancer stem cell development and tumor progression and invasiveness (Fig. 5A) (42)(43)(44)(45)(46)(47)(48)(49). Interestingly, the most enriched Gene Ontology (GO) terms included cell differentiation, proliferation, and locomotor activity (Fig.…”

Section: Abx Therapy Induces a Cancer Stem Cell Phenotype In Id8 Eoc Tumors In Nsg Micementioning

confidence: 99%

Disruption of the Gut Microbiota Attenuates Epithelial Ovarian Cancer Sensitivity to Cisplatin Therapy

Chambers

Esakov

Braley

et al. 2021

Preprint

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Background: Epithelial Ovarian Cancer (EOC) is the second most common gynecologic malignancy in the United States, but the leading cause of gynecologic cancer death. Despite many achieving remission with first-line therapy, up to 80% of patients will recur and require additional treatment. Antibiotic therapy is frequently used during cancer treatments for both prophylaxis and treatment of infections, although this profoundly impacts the gut microbiome. Multiple studies suggest that an unperturbed gut microbiome may provide a protective microenvironment, and disruption may be permissive to tumor growth and chemotherapy resistance, including platinum agents. Experimental Design: We assessed whether antibiotic therapy would impact growth of EOC and sensitivity to cisplatin in murine models. Immune competent or compromised mice were given control or antibiotic (ABX) containing water (metronidazole, ampicillin, vancomycin, and neomycin) for two weeks before being intraperitoneally injected with murine ID8 or ID8-VEGF EOC cells. Tumors were monitored and cisplatin therapy was administered weekly until endpoint. Stool was collected throughout the study to assess for microbial population effects over time. Cecal microbiota transplants (CMTs) of contents derived from ABX or control treated donor mice were performed on ABX treated recipient mice. Results: Both immune competent and immune compromised ID8 and ID8 VEGF tumor-bearing mice demonstrated a decreased response to cisplatin therapy in ABX treated groups with an increase in overall tumor burden. RNAseq analysis showed enrichment of multiple cell proliferation and stem cell pathways, and stem cell genes SOX2, WNT and PAX2. The self-renewal of cancer cells derived from tumors of ABX treated mice was increased compared to tumors from control mice, indicative of a microbiota derived tumor suppressor. Conclusion: Collectively, these studies indicate an intact microbiome provides a tumor suppressor and maintains chemosensitivity that is disrupted by ABX treatment.

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Section: Abx Therapy Induces a Cancer Stem Cell Phenotype In Id8 Eoc Tumors In Nsg Micementioning

confidence: 99%

Disruption of the Gut Microbiota Attenuates Epithelial Ovarian Cancer Sensitivity to Cisplatin Therapy

Chambers

Esakov

Braley

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…[25][26][27][28] CD9-high AML LSCs represent a subgroup of cells with the potential to promote tumor growth and to reconstitute human AML in immunocompromised mice. 29 CD9 has been suggested to be a negative prognostic marker in pediatric BCP-ALL, 30 and it is associated with poor complete remission. 27 Conflicting results have been reported for AML, 26,31 highlighting the importance of understanding the role of CD9 in leukemia.…”

Section: Introductionmentioning

confidence: 99%

A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

Kollmann

Grausenburger

Klampfl

et al. 2021

Blood

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The transcription factors STAT5A and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9. Levels of CD9 represent a prognostic marker for patients with STAT5-driven leukemia and our findings suggest that anti-CD9 antibodies may be useful in their treatment to target and eliminate LSCs. We show that it is vital to consider STAT5A and STAT5B as distinct entities in normal and malignant hematopoiesis.

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CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

Cited by 2 publications

References 41 publications

Disruption of the Gut Microbiota Attenuates Epithelial Ovarian Cancer Sensitivity to Cisplatin Therapy

Disruption of the Gut Microbiota Attenuates Epithelial Ovarian Cancer Sensitivity to Cisplatin Therapy

A STAT5B–CD9 axis determines self-renewal in hematopoietic and leukemic stem cells

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