Echinomycin protects mice against relapsed acute myeloid leukemia without adverse effect on hematopoietic stem cells
Open accessAbstract
Acute myeloid leukemia (AML) often relapses following chemotherapy-induced remission and is generally chemo-resistant. Given the potential role for cancer stem cells in relapse, targeting of the leukemia-initiating cell (LIC) in AML may provide improved outcome following remission induction. However, due to overlap in their self-renewal program with normal hematopoietic stem cells (HSCs), therapeutic targeting of the LIC may have an adverse effect on long-term hematopoietic recovery. Here we used a mouse model of relapsed AML to explore whether the hypoxia-inducible factor (HIF)1α inhibitor echinomycin can be used to treat relapsed AML without affecting host HSCs. We show that echinomycin cured 40% to 60% of mice transplanted with relapsed AML. Bone marrow cells from the cured mice displayed normal composition of HSCs and their progenitors and were as competent as those isolated from nonleukemic mice in competitive repopulation assays. Importantly, in mice with complete remission, echinomycin appeared to completely eliminate LICs because no leukemia could be propagated in vivo following serial transplantation. Taken together, our data demonstrate that in a mouse model of relapsed AML, low-dose echinomycin selectively targets LICs and spares normal hematopoiesis.
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Echinomycin dissolved in DMSO is active against leukemia in mice.
“We have demonstrated that echinomycin, dissolved in dimethyl sulfoxide (DMSO) is active against leukemia in mice24, 25.”
From Liposomal Formulation of HIF-1α Inhibitor Echinomycin Eliminates Established Metastases of Triple-negative Breast Cancer (2020) · cites this paper as [24]
The Results report that echinomycin was effective against relapsed AML in mice, with longer survival than in vehicle-treated mice. Our copy does not say that the echinomycin given to mice was dissolved in DMSO; the Materials and methods passage mentioning dimethylsulfoxide uses it to dissolve crystals in a cell-viability assay, not to prepare the treatment. (LLM, conf=0.88)
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References 48 · Cited by 69
- Authors
- Wang, Y., Liu, Y., Tang, F., Bernot, K. M., Schore, R., Marcucci, G., Caligiuri, M. A., Zheng, P., & Liu, Y.
- Affiliations
- Children's National (US)
- North Carolina Agricultural and Technical State University (US)
- The Ohio State University (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2014-08-14
- Volume
- 124
- Issue
- 7
- Pages
- 1127-1135
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC4133485
- OpenAlex
- W2064770926
- Cited by
- 69
- References
- 48
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 5 · 2022: 3 · 2021: 11 · 2020: 8 · 2019: 5 · 2018: 8 · 2017: 5 · 2016: 5 · 2015: 5
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA89341, P50CA140158, R01CA089341, U01CA183030, R01CA058033, CA140158, R21CA164469, R01CA171972)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- echinomycin, acute myeloid leukemia, relapsed leukemia, leukemia-initiating cells, cancer stem cells, hypoxia-inducible factor-1α, hematopoietic stem cells, hematopoietic recovery, competitive repopulation, serial transplantation, chemoresistance
- MeSH terms
- Acute Disease, Animals, Antibiotics, Antineoplastic, Echinomycin, Flow Cytometry, Hematopoietic Stem Cells, Leukemia, Myeloid, Neoplasm Recurrence, Local, Remission Induction, Time Factors, Neoplastic Stem Cells, Bone Marrow Transplantation, Treatment Outcome, Mice, Knockout, RNA Interference, Hypoxia-Inducible Factor 1, alpha Subunit
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