RNAi prodrugs decrease elevated mRNA levels of Polo‐like kinase 1 in ex vivo cultured primary cells from pediatric acute myeloid leukemia patients

Abstract

Acute myeloid leukemia (AML) is a genetically heterogeneous disease that originates from mutations in the myeloid compartment of hematopoietic cells. Of all leukemia types, AML is the most refractory to treatment and the five-year survival ranges from 40% in adults to about 70% in children. 1 Induction treatment-resistant and relapsing cases have poor prognosis. 2,3 The high incidence of treatment-related deaths indicates that the use of chemotherapy has reached its limits and other treatment options should be developed to cure more patients. 4,5 Allogeneic stem cell transplantation is one of the approaches that is used in AML when other therapy options are exhausted. 6 Moreover, pediatric patients who recover

Thermal proteome profiling identifies PIP4K2A and ZADH2 as off‐targets of Polo‐like kinase 1 inhibitor volasertib

“…Several studies have demonstrated that PLK2 and PLK3 have tumor‐suppressive roles, therefore, their inhibition needs to be evaluated for some tumors and especially for normal cells. In hematological cancers, however, these PLKs are frequently silenced as we observed in T‐ALL, B‐ALL, and AML 12,24,35‐37 . In particular, the Jurkat cell lines do not express either of them, 24 confirmed by the TPP analysis (data not shown).…”

“…In hematological cancers, however, these PLKs are frequently silenced as we observed in T-ALL, B-ALL, and AML. 12,24,[35][36][37] In particular, the Jurkat cell lines do not express either of them, 24 confirmed by the TPP analysis (data not shown). Therefore, we could not assess how their T agg changes upon volasertib and onvansertib treatment.…”

Polo-like kinase 1 Decrease During Induction Therapy Could Indicate Good Treatment Response, Favorable Risk Stratification, and Prolonged Survival in Pediatric Acute Lymphoblastic Leukemia: [RETRACTED]

“…PLK1 is overexpressed in various hematological malignancies, according to previous studies 17,24,25 . A study claims that PLK1 in peripheral blood and BMMCs is higher in pediatric AML patients than in healthy controls 24 .…”

“…17,24,25 A study claims that PLK1 in peripheral blood and BMMCs is higher in pediatric AML patients than in healthy controls. 24 PLK1 in peripheral blood leukocytes is also increased in chronic myeloid leukemia patients compared with healthy controls. 25 In pediatric ALL patients, the dysregulation of PLK1 is still controversial.…”

“…PLK1 is overexpressed in various hematological malignancies, according to previous studies. 17,24,25 A study claims that PLK1 in peripheral blood and BMMCs is higher in pediatric AML patients than in healthy controls. 24 PLK1 in peripheral blood leukocytes is also increased in chronic myeloid leukemia patients compared with healthy controls.…”