Locations:
Search IconSearch
October 8, 2019/Cancer

Drug Repurposing for the Treatment of Childhood Leukemia

The effect of mefloquine on acute leukemia cell lines

650×450-Corey-drug-research

By Seth Corey, MD, MPH

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Many patients with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) of childhood suffer significant adverse effects from conventional chemotherapy agents. Therapy-related toxicities include tumor lysis syndrome, thrombosis, bleeding, infection, mucositis, pancreatitis and hypoglycemia. As a result, we continue to seek additional therapies with less toxicity.

Drug repurposing

Many drugs used to treat adults have not been tested in patients under 18 years old. Developing new drugs is an expensive and time-consuming undertaking, especially for pediatric conditions for which small numbers of patients prevent the economic viability of phase 1 clinical trials. Drug repurposing is one way to speed the process, getting new anti-leukemic agents to market—and to the children who need them—safely and efficiently. In drug repurposing, we test therapies that have already proven to be safe in children, with well-established toxicity profiles and pharmacogenomics as potential agents in different diseases.

One drug with the potential to be repurposed is mefloquine, which previous research has already identified a potential agent against leukemia cells. Mefloquine, an antimalarial drug, may target the process of autophagy in leukemia cells — a survival, recycling mechanism promoting cancer proliferation. We recently completed a study of the in vitro efficacy and mechanism of mefloquine on acute leukemia cell lines.

Preclinical work establishes the efficacy of an old drug for a new indication. Since we already know the toxicity profile of mefloquine, our goal in this research is to whether and how the medication is effective. In this study, we sought to observe cell proliferation, viability, apoptosis and autophagy in AML and ALL cell lines treated with mefloquine. This study was presented at the 2019 American Society of Pediatric Hematology/Oncology Conference in New Orleans.

Advertisement

Mefloquine achieves cell death

We treated AML and ALL cell lines (i.e., NB4 [promyelocytic], U937 [monoblastic], Thp-1 [monoblastic] and Jurkat [T-lymphoblastic) with mefloquine. We measured cell proliferation using the 3-(4,5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) colorimetric assay and cell viability using the trypan blue (TB) assay. We performed Western blotting on NB4 and U937 cell lines using apoptosis markers PARP-1 and Caspase-3, autophagy markers Atg7, Atg5, P62 and LC3B, and ER stress marker CHOP.

Our hypothesis was that treatment of the cell lines with mefloquine would decrease cell proliferation and viability by targeting autophagy and inducing apoptosis. The MTT assay revealed decreased metabolic activity of the leukemic cells.

We also observed decreased cell proliferation and viability. The leukemic cells did not die from a caspase 3-dependent mechanism.

Our study suggests mefloquine is a potential drug for the treatment of leukemia; however, further investigation is required to determine the mechanism by which it targets autophagy.

Next steps

Our next step in repurposing mefloquine is to secure funding for critical in vivo trials in order to obtain the late pre-clinical data necessary for a successful investigational drug application.

Advertisement

Related Articles

Surgeon
June 30, 2025/Cancer/News & Insight
Potential for Deintensification of Surgical Interventions in Low-Risk Breast Cancer

Reconsidering axillary lymph node dissection as well as depth of surgical margins

Dendritic cell
June 26, 2025/Cancer/News & Insight
Avelumab Induces Natural Killer Cell Activation and Dendritic Cell Crosstalk

Researchers uncover profound differences in the mechanism of action between different PD-L1 checkpoint inhibitors

World map
June 19, 2025/Cancer/News & Insight
Breaking Barriers to Cancer Care: Cleveland Clinic’s Global Approach

A multi-pronged strategy for tackling cancer access problems

CAR T-cell therapy illustration
June 12, 2025/Cancer/News & Insight
First-Ever U.S. Trial of CAR T-Cell Therapy for Relapsed/Refractory AL Amyloidosis

Early results show patients experiencing deep and complete response

Genomic profiling
June 10, 2025/Cancer
Cleveland Clinic’s Hemato-Oncology Team Spearheads the Development of Guidelines for Genomic Profiling of MDS to Inform Allo-HCT

Inclusion of genomic profiling and risk factors recommended for treatment planning

scan showing cholangiocarcinoma
June 5, 2025/Cancer/News & Insight
Exploring Novel Therapeutic Avenues in Advanced Cholangiocarcinoma: Lessons from the EA2187 Trial

Collaborative research effort underscores the urgent need for effective second-line therapies in this rare, aggressive cancer

Anticoagulant sign
June 4, 2025/Cancer/News & Insight
Direct-Acting Oral Anticoagulants Safe for Patients with Brain Metastasis

Largest study to date comparing direct-acting oral anticoagulants to low-molecular-weight heparin

Ad