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Communication

Novel Polyethylene Glycol-Conjugated Triazole Derivative with High Thyrointegrin αvβ3 Affinity in Acute Myeloid Leukemia Management

1
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA
2
Hematology Unit, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
3
Albany Medical Center, Pathology Department, AMC Hospital, Albany, NY 12208, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Pau Montesinos
Cancers 2021, 13(16), 4070; https://doi.org/10.3390/cancers13164070
Received: 26 July 2021 / Revised: 5 August 2021 / Accepted: 10 August 2021 / Published: 13 August 2021
(This article belongs to the Special Issue Acute Myeloid Leukemia (AML))
The integrin αvβ3 antagonist (P-bi-TAT) is associated with the downregulation of signaling pathways, especially NF-κB pathway, which play an important role in leukemogenesis. Our results provide a rationale for further evaluation of the αvβ3 antagonists as providing potential therapeutic utility not only in AML but also in different malignancies.
(1) Background: Acute myeloid leukemia (AML) accounts for up to one-third of more than 60,000 leukemia cases diagnosed annually in the U.S. Primary AML cells express membrane αvβ3 integrin, which is associated with adverse prognosis and resistance to chemotherapies. A novel anticancer compound Polyethylene glycol-conjugated bi-TriAzole Tetraiodothyroacetic acid (P-bi-TAT) interacts with high affinity (Ki 0.3 nM) and specificity with the thyrointegrin αvβ3. We evaluated P-bi-TAT activities in two different AML models representing monocytic and myelocytic forms of acute leukemia. (2) Methods and Results: The in vivo AML models were established prior to initiation of treatment protocols by grafting human leukemia cells in immunocompromised mice. IVIS imaging scans revealed that leukemic colonies were extensively established throughout the bone marrow, liver, and lung of the untreated animals. In animals treated with P-bi-TAT at daily doses ranging from 1–10 mg/kg, subcutaneously for 2–3 weeks, IVIS imaging scans revealed 95% reduction in bone marrow colonies and leukemic colonies in liver and lung. Also, the leukemic cells were not detected in bone marrow samples of P-bi-TAT-treated animals. The anti-neoplastic effect of P-bi-TAT administration on leukemic cells was associated with marked inhibition of NF-κB activity. We conclude that experimental P-bi-TAT therapy in vivo appears extraordinarily effective against the two forms of human AML models in mice. Because the P-bi-TAT molecular target, thyrointegrin αvβ3, is consistently expressed in many, if not all, clinical AML samples, P-bi-TAT-based therapy seems to have significant clinical potential in treating most AML sub-types. Hence, P-bi-TAT represents a promising targeted therapeutic agent for AML patients. View Full-Text
Keywords: thyrointegrin receptor; αvβ3; P-bi-TAT; leukemia; AML therapy thyrointegrin receptor; αvβ3; P-bi-TAT; leukemia; AML therapy
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MDPI and ACS Style

Sudha, T.; Godugu, K.; Darwish, N.H.E.; Nazeer, T.; Mousa, S.A. Novel Polyethylene Glycol-Conjugated Triazole Derivative with High Thyrointegrin αvβ3 Affinity in Acute Myeloid Leukemia Management. Cancers 2021, 13, 4070. https://doi.org/10.3390/cancers13164070

AMA Style

Sudha T, Godugu K, Darwish NHE, Nazeer T, Mousa SA. Novel Polyethylene Glycol-Conjugated Triazole Derivative with High Thyrointegrin αvβ3 Affinity in Acute Myeloid Leukemia Management. Cancers. 2021; 13(16):4070. https://doi.org/10.3390/cancers13164070

Chicago/Turabian Style

Sudha, Thangirala, Kavitha Godugu, Noureldien H.E. Darwish, Tipu Nazeer, and Shaker A. Mousa. 2021. "Novel Polyethylene Glycol-Conjugated Triazole Derivative with High Thyrointegrin αvβ3 Affinity in Acute Myeloid Leukemia Management" Cancers 13, no. 16: 4070. https://doi.org/10.3390/cancers13164070

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