Version 1
: Received: 23 March 2021 / Approved: 24 March 2021 / Online: 24 March 2021 (17:37:56 CET)
Version 2
: Received: 4 October 2021 / Approved: 6 October 2021 / Online: 6 October 2021 (15:07:27 CEST)
How to cite:
Mendivil-Perez, M.; Velez-Pardo, C.; Quiroz-Duque, L.M.; Restrepo-Rincon, A.; Valencia-Zuluaga, N.A.; Jimenez-Del-Rio, M. TPEN Selectively Eliminates Lymphoblastic B cells from Bone Marrow Pediatric Acute Lymphoblastic Leukemia Patients. Preprints2021, 2021030611. https://doi.org/10.20944/preprints202103.0611.v2
Mendivil-Perez, M.; Velez-Pardo, C.; Quiroz-Duque, L.M.; Restrepo-Rincon, A.; Valencia-Zuluaga, N.A.; Jimenez-Del-Rio, M. TPEN Selectively Eliminates Lymphoblastic B cells from Bone Marrow Pediatric Acute Lymphoblastic Leukemia Patients. Preprints 2021, 2021030611. https://doi.org/10.20944/preprints202103.0611.v2
Mendivil-Perez, M.; Velez-Pardo, C.; Quiroz-Duque, L.M.; Restrepo-Rincon, A.; Valencia-Zuluaga, N.A.; Jimenez-Del-Rio, M. TPEN Selectively Eliminates Lymphoblastic B cells from Bone Marrow Pediatric Acute Lymphoblastic Leukemia Patients. Preprints2021, 2021030611. https://doi.org/10.20944/preprints202103.0611.v2
APA Style
Mendivil-Perez, M., Velez-Pardo, C., Quiroz-Duque, L.M., Restrepo-Rincon, A., Valencia-Zuluaga, N.A., & Jimenez-Del-Rio, M. (2021). TPEN Selectively Eliminates Lymphoblastic B cells from Bone Marrow Pediatric Acute Lymphoblastic Leukemia Patients. Preprints. https://doi.org/10.20944/preprints202103.0611.v2
Chicago/Turabian Style
Mendivil-Perez, M., Natalia Andrea Valencia-Zuluaga and Marlene Jimenez-Del-Rio. 2021 "TPEN Selectively Eliminates Lymphoblastic B cells from Bone Marrow Pediatric Acute Lymphoblastic Leukemia Patients" Preprints. https://doi.org/10.20944/preprints202103.0611.v2
Abstract
B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N’, N’-tetrakis(2-pyridylmethyl)-ethylenediamine).is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cells. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), in vitro. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n=3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
6 October 2021
Commenter:
Marlene Jimenez-Del-Rio
Commenter's Conflict of Interests:
Author
Comment:
Changes: 1. The title has changed to "TPEN Selectively Eliminates Lymphoblastic B cells from Bone Marrow Pediatric Acute Lymphoblastic Leukemia Patients"; 2. Three new samples from nonleukemic subjects have now been included in Fig 2-6. Therefore, the abstract has been modified; Statistical analysis has been corrected in the table and in Fig 2-6; Results have been modified. 3. Discussion is now more robust with the new addition of 3 non-leukemic samples.
Commenter: Marlene Jimenez-Del-Rio
Commenter's Conflict of Interests: Author