ABT199/venetoclax synergism with thiotepa enhances cytotoxicity of chemo drugs in AML cells

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A caller investigation insubstantial was published successful Oncotarget's Volume 15 connected March 14, 2024, entitled, "ABT199/venetoclax synergism pinch thiotepa enhances nan cytotoxicity of fludarabine, cladribine and busulfan successful AML cells."

ABT199/venetoclax, an inhibitor of nan pro-survival BCL-2 protein, has improved AML treatment. Its efficacy successful hematopoietic stem compartment transplantation (HSCT), erstwhile mixed pinch different chemotherapeutic drugs, has not been thoroughly investigated. In this caller study, researchers Benigno C. Valdez, Bin Yuan, David Murray, Jeremy L. Ramdial, Uday Popat, Yago Nieto, and Borje S. Andersson from The University of Texas MD Anderson Cancer Center and nan University of Alberta show nan synergistic cytotoxicity of ABT199/venetoclax pinch nan DNA alkylator thiotepa (Thio) successful AML cells. 

"The results whitethorn supply applicable accusation for nan creation of objective tests utilizing these narcotics to circumvent recognized drug-resistance mechanisms erstwhile utilized arsenic portion of pre-transplant conditioning regimens for AML patients undergoing allogenic HSCT."

Cleavage of Caspase 3, PARP1 and HSP90, arsenic good arsenic accrued Annexin V positivity, propose potent activation of apoptosis by this two-drug combination; accrued levels of γ-H2AX, P-CHK1 (S317), P-CHK2 (S19) and P-SMC1 (S957) bespeak an enhanced DNA harm response. Likewise, nan accrued level of P-SAPK/JNK (T183/Y185) and decreased P-PI3Kp85 (Y458) propose enhanced activation of accent signaling pathways. These molecular readouts were synergistically enhanced erstwhile ABT199/venetoclax and Thio were mixed pinch fludarabine, cladribine and busulfan. 

The five-drug operation decreased nan levels of BCL-2, BCL-xL and MCL-1, suggesting its imaginable objective relevance successful overcoming ABT199/venetoclax resistance. Moreover, this operation is progressive against P53-negative and FLT3-ITD-positive compartment lines. Enhanced activation of apoptosis was observed successful leukemia patient-derived compartment samples exposed to nan five-drug combination, suggesting a objective relevance. 

"The results supply a rationale for objective tests utilizing these two- and five-drug combinations arsenic portion of a conditioning regimen for AML patients undergoing HSCT."


Journal reference:

Valdez, B. C., et al. (2024). ABT199/venetoclax synergism pinch thiotepa enhances nan cytotoxicity of fludarabine, cladribine and busulfan successful AML cells. Oncotarget. doi.org/10.18632/oncotarget.28563.

Posted in: Medical Research News | Medical Condition News

Tags: Acute Myeloid Leukemia, Apoptosis, Cancer, Cell, Cladribine, Cytotoxicity, DNA, DNA Damage, Drugs, Efficacy, Flu, Leukemia, Myeloid Leukemia, Oncology, Protein, Research, Stress, Transplant