Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

TPEN Selectively Eliminates Lymphoblastic B Cells from Pediatric Acute Lymphoblastic Lleukemia Patients

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 Pediatric Acute Lymphoblastic Lleukemia Patients. Preprints 2021, 2021030611 (doi: 10.20944/preprints202103.0611.v1). 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 Pediatric Acute Lymphoblastic Lleukemia Patients. Preprints 2021, 2021030611 (doi: 10.20944/preprints202103.0611.v1).

Abstract

B-acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by abnormal proliferation and accumulation of immature B-lymphoblast arrested at various differentiation stages. Despite some advances in treatment, there is still an important percentage of pediatric patients with precursor-B ALL who relapsed. Therefore, alternative therapies are needed to improve cure rates for pediatric patients. TPEN is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cells. Consequently, TPEN has been suggested as a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like milieu e.g., bloodstream and bone marrow (BM) in vivo. In this investigation, we report for the first time that TPEN significantly induces apoptosis in CD34+/CD19+ cells from whole bone marrow de novo B-ALL (n=5) and refractory B-ALL (n=6) patients by oxidative stress (OS, n=8). We found that TPEN significantly increased not only positive cell counts for the oxidation of the stress sensor protein DJ-1 as a sign of the formation of H2O2, but also significantly increased positive cell counts for the proapoptotic protein TP53, PUMA, and CASPASE-3 as indicative of apoptosis in B-ALL cells irrespective of diagnostic status (de novo or refractory) and sex. Understanding the TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic prooxidant-inducing anticancer agents.

Keywords

Acute leukemia; CASPASE-3; chemoresistant; DJ-1; TP53; PUMA; reactive oxygen species; signaling; TPEN

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