Furosemide‑induced eradication of myeloblasts via the inhibition of tumor necrosis factor‑&alpha; expression in a patient with acute biphenotypic leukemia: A case report

Chang,Yu-Wei; Chao,Wan-Ru; Lai,Yen-Ting; Fan,Frank Sheng

doi:10.3892/ol.2024.14711

Furosemide‑induced eradication of myeloblasts via the inhibition of tumor necrosis factor‑α expression in a patient with acute biphenotypic leukemia: A case report

Authors:
- Yu-Wei Chang
- Wan-Ru Chao
- Yen-Ting Lai
- Frank Sheng Fan
View Affiliations

Affiliations: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 402306, Taiwan, R.O.C., Department of Pathology, Chung Shan Medical University Hospital, Taichung 402306, Taiwan, R.O.C., Division of Hematology and Oncology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402306, Taiwan, R.O.C.
Published online on: October 1, 2024 https://doi.org/10.3892/ol.2024.14711
Article Number: 578
Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study reports the potential of furosemide therapeutic activity in acute myeloid leukemia. A 26‑year‑old man with acute biphenotypic leukemia was treated with furosemide for suspected pulmonary edema, which was later deemed to be an infiltration of leukemia cells. Notably, the myeloblast population was rapidly eliminated during furosemide therapy. Bone marrow specimens biopsied at different time points were used for immunohistochemical analysis of the expression levels of tumor necrosis factor‑α (TNF‑α) and its two receptors, TNF‑α receptors 1 and 2. The expression of TNF‑α and its receptors in the bone marrow was markedly suppressed by furosemide, along with the elimination of the myeloblasts. Thus, it was hypothesized that the growth of myeloblasts in the patient depended on autocrine and/or paracrine TNF‑α stimulation, whereas furosemide disrupted this positive feedback loop. Therefore, furosemide is suggested as an effective therapeutic agent for acute myeloid leukemia, at least as an adjunct to standard chemotherapy and gene‑targeted therapy.

View Figures

View References

1	Balkwill F: Tumour necrosis factor and cancer. Nat Rev Cancer. 9:361–371. 2009. View Article : Google Scholar : PubMed/NCBI
2	Tian T, Wang M and Ma D: TNF-alpha, a good or bad factor in hematological diseases? Stem Cell Investig. 1:122014.PubMed/NCBI
3	Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, Lee SR and Yang SH: the role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics. Int J Mol Sci. 22:27192021. View Article : Google Scholar : PubMed/NCBI
4	Williams GM: Antitumor necrosis factor-alpha therapy and potential cancer inhibition. Eur J Cancer Prev. 17:169–177. 2008. View Article : Google Scholar : PubMed/NCBI
5	Bryniarski P, Nazimek K and Marcinkiewicz J: Immunomodulatory potential of diuretics. Biology (Basel). 10:13152021.PubMed/NCBI
6	Weinberg OK and Arber DA: How I diagnose acute leukemia of ambiguous lineage. Am J Clin Pathol. 158:27–34. 2022. View Article : Google Scholar : PubMed/NCBI
7	Binder S, Luciano M and Horejs-Hoeck J: The cytokine network in acute myeloid leukemia (AML): A focus on pro- and anti-inflammatory mediators. Cytokine Growth Factor Rev. 43:8–15. 2018. View Article : Google Scholar : PubMed/NCBI
8	Zhou X, Li Z and Zhou J: Tumor necrosis factor α in the onset and progression of leukemia. Exp Hematol. 45:17–26. 2017. View Article : Google Scholar : PubMed/NCBI
9	Hoang T, Levy B, Onetto N, Haman A and Rodriguez-Cimadevilla JC: Tumor necrosis factor alpha stimulates the growth of the clonogenic cells of acute myeloblastic leukemia in synergy with granulocyte/macrophage colony-stimulating factor. J Exp Med. 170:15–26. 1989. View Article : Google Scholar : PubMed/NCBI
10	Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y and Kurokawa M: Positive feedback between NF-κB and TNF-α promotes leukemia-initiating cell capacity. J Clin Invest. 124:528–542. 2014. View Article : Google Scholar : PubMed/NCBI
11	Verma S, Singh A, Yadav G, Kushwaha R, Ali W, Verma SP and Singh US: Serum tumor necrosis factor-alpha levels in acute leukemia and its prognostic significance. Cureus. 14:e248352022.PubMed/NCBI
12	Tuttolomondo A, Pinto A, Di Raimondo D, Corrao S, Di Sciacca R, Scaglione R, Caruso C and Licata G: Changes in natriuretic peptide and cytokine plasma levels in patients with heart failure, after treatment with high dose of furosemide plus hypertonic saline solution (HSS) and after a saline loading. Nutr Metab Cardiovasc Dis. 21:372–379. 2011. View Article : Google Scholar : PubMed/NCBI
13	Tuttolomondo A, Di Raimondo D, Bellia C, Clemente G, Pecoraro R, Maida C, Simonetta I, Vassallo V, Di Bona D, Gulotta E, et al: Immune-Inflammatory and metabolic effects of high dose furosemide plus hypertonic saline solution (HSS) treatment in cirrhotic subjects with refractory ascites. PLoS One. 11:e01654432016. View Article : Google Scholar : PubMed/NCBI
14	Xu B, Thornton C, Makris A, Ogle R and Hennessy A: Anti-hypertensive drugs alter cytokine production from preeclamptic placentas and peripheral blood mononuclear cells. Hypertens Pregnancy. 26:343–356. 2007. View Article : Google Scholar : PubMed/NCBI
15	Xu B, Makris A, Thornton C, Ogle R, Horvath JS and Hennessy A: Antihypertensive drugs clonidine, diazoxide, hydralazine and furosemide regulate the production of cytokines by placentas and peripheral blood mononuclear cells in normal pregnancy. J Hypertens. 24:915–922. 2006. View Article : Google Scholar : PubMed/NCBI
16	Yuengsrigul A, Chin TW and Nussbaum E: Immunosuppressive and cytotoxic effects of furosemide on human peripheral blood mononuclear cells. Ann Allergy Asthma Immunol. 83:559–566. 1999. View Article : Google Scholar : PubMed/NCBI
17	Dong QM, Ling C, Chen X and Zhao LI: Inhibition of tumor necrosis factor-α enhances apoptosis induced by nuclear factor-κB inhibition in leukemia cells. Oncol Lett. 10:3793–3798. 2015. View Article : Google Scholar : PubMed/NCBI
18	Zhou X, Zhou S, Li B, Li Q, Gao L, Li D, Gong Q, Zhu L, Wang J, Wang N, et al: Transmembrane TNF-α preferentially expressed by leukemia stem cells and blasts is a potent target for antibody therapy. Blood. 126:1433–1442. 2015. View Article : Google Scholar : PubMed/NCBI
19	Wang Z, Vilekar P, Huang J and Weaver DF: Furosemide as a probe molecule for the treatment of neuroinflammation in Alzheimer's disease. ACS Chem Neurosci. 11:4152–4168. 2020. View Article : Google Scholar : PubMed/NCBI
20	Wang Z, Wang Y, Vilekar P, Yang SP, Gupta M, Oh MI, Meek A, Doyle L, Villar L, Brennecke A, et al: Small molecule therapeutics for COVID-19: Repurposing of inhaled furosemide. PeerJ. 8:e95332020. View Article : Google Scholar : PubMed/NCBI