Lei Wang1, Wenjun Zhang2, Yi Ding2, Bing Xiu2, Ping Li2, Yan Dong2, Qi Zhu1, Aibin Liang2. 1. Department of Hematology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine 639 Zhizaoju Road, Shanghai 200011, China. 2. Department of Hematology, Tongji Hospital of Tongji University 389 Xincun Road, Shanghai 200065, China.
Abstract
OBJECTIVE: To analyze the causative mechanisms in refractory leukemia cells. METHODS: Vascular endothelial growth factor (VEGF) blood plasma concentrations in 35 de novo, 6 relapse, 20 remission leukemia patients and 10 healthy kids were determined via ELISA analyses. Transcription levels of the VEGF receptors (VEGFR) Fms-like tyrosine kinase-1 (Flt-1) and kinase-domain insert containing receptor (KDR) were determined in participants' leucocytes with RT-PCR. Apoptosis rates as well as Cyt-C and Caspase-3 expression was determined in Jurkat, Jurkat(Bcl-2), healthy and recurrent leukemia leukocytes with and without VP-16 applications via flow cytometry. Total Akt (t-Akt) expression and its phosphorylation (p-AKT) status in leukocytes of the participants were analyzed with western blots. RESULTS: Healthy children and the remission group had the lowest blood plasma VEGF concentrations (91.16±41.34 vs. 135.80±111.28 pg/ml), followed by de novo leukemia patients (362.49±195.68 pg/ml-494.19±186.23 pg/ml) and relapse patients (574.37±278.45 pg/ml) (P<0.01). The same trend was statistically significant visible for Flt-1 and KDR expressions in leukocytes of the participants. Stable Bcl-2 overexpression led to reduced apoptosis rates as well as Cyt-C and Caspase-3 expressions in Jurkat cells after VP-16 application, which was similar in leucocytes of remission patients. In contrast to no phosphorylation in healthy children, Akt was phosphorylated in 10% remission samples, 30% de novo leukemia samples and in 67% of recurrent leukemia leucocytes. CONCLUSION: High VEGF plus VEGFR expression and AKT phosphorylation are highest in leukocytes of remission patients, suggesting VEGF signaling as a cause of reduced apoptosis susceptibility upon treatments.
OBJECTIVE: To analyze the causative mechanisms in refractory leukemia cells. METHODS:Vascular endothelial growth factor (VEGF) blood plasma concentrations in 35 de novo, 6 relapse, 20 remission leukemiapatients and 10 healthy kids were determined via ELISA analyses. Transcription levels of the VEGF receptors (VEGFR) Fms-like tyrosine kinase-1 (Flt-1) and kinase-domain insert containing receptor (KDR) were determined in participants' leucocytes with RT-PCR. Apoptosis rates as well as Cyt-C and Caspase-3 expression was determined in Jurkat, Jurkat(Bcl-2), healthy and recurrent leukemia leukocytes with and without VP-16 applications via flow cytometry. Total Akt (t-Akt) expression and its phosphorylation (p-AKT) status in leukocytes of the participants were analyzed with western blots. RESULTS: Healthy children and the remission group had the lowest blood plasma VEGF concentrations (91.16±41.34 vs. 135.80±111.28 pg/ml), followed by de novo leukemiapatients (362.49±195.68 pg/ml-494.19±186.23 pg/ml) and relapse patients (574.37±278.45 pg/ml) (P<0.01). The same trend was statistically significant visible for Flt-1 and KDR expressions in leukocytes of the participants. Stable Bcl-2 overexpression led to reduced apoptosis rates as well as Cyt-C and Caspase-3 expressions in Jurkat cells after VP-16 application, which was similar in leucocytes of remission patients. In contrast to no phosphorylation in healthy children, Akt was phosphorylated in 10% remission samples, 30% de novo leukemia samples and in 67% of recurrent leukemia leucocytes. CONCLUSION: High VEGF plus VEGFR expression and AKT phosphorylation are highest in leukocytes of remission patients, suggesting VEGF signaling as a cause of reduced apoptosis susceptibility upon treatments.
Authors: M Broggini; S V Marchini; E Galliera; P Borsotti; G Taraboletti; E Erba; M Sironi; J Jimeno; G T Faircloth; R Giavazzi; M D'Incalci Journal: Leukemia Date: 2003-01 Impact factor: 11.528
Authors: Luciana M Gutiérrez; Matías Valenzuela Alvarez; Yuanzheng Yang; Fiorella Spinelli; María José Cantero; Laura Alaniz; Mariana G García; Eugenie S Kleinerman; Alejandro Correa; Marcela F Bolontrade Journal: Apoptosis Date: 2021-05-22 Impact factor: 4.677