scholarly journals Targeted leukaemia therapy: a chemotherapy-free future?

2021 ◽  
Vol 8 (1) ◽  
pp. e1
Author(s):  
The Lancet Haematology
Keyword(s):  
2015 ◽  
Vol 17 (1) ◽  
pp. 30-41 ◽  
Author(s):  
Félix Sauvage ◽  
Gillian Barratt ◽  
Lars Herfindal ◽  
Juliette Vergnaud-Gauduchon

Drug Safety ◽  
2002 ◽  
Vol 25 (15) ◽  
pp. 1057-1077 ◽  
Author(s):  
Claudia Langebrake ◽  
Dirk Reinhardt ◽  
J??rg Ritter

2011 ◽  
Vol 439 (3) ◽  
pp. 453-470 ◽  
Author(s):  
Wen-Hsin Liu ◽  
Long-Sen Chang

The present study was conducted to verify whether caffeine is beneficial for improving leukaemia therapy. Co-treatment with adaphostin (a Bcr/Abl inhibitor) was found to potentiate caffeine-induced Fas/FasL up-regulation. Although adaphostin did not elicit ASK1 (apoptosis signal-regulating kinase 1)-mediated phosphorylation of p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase), co-treatment with adaphostin notably increased p38 MAPK/JNK activation in caffeine-treated cells. Suppression of p38 MAPK and JNK abrogated Fas/FasL up-regulation in caffeine- and caffeine/adaphostin-treated cells. Compared with caffeine, adaphostin markedly suppressed Akt/ERK (extracellular-signal-regulated kinase)-mediated MKP-1 (MAPK phosphatase 1) protein expression in K562 cells. MKP-1 down-regulation eventually elucidated the enhanced effect of adaphostin on p38 MAPK/JNK activation and subsequent Fas/FasL up-regulation in caffeine-treated cells. Knockdown of p38α MAPK and JNK1, ATF-2 (activating transcription factor 2) and c-Jun by siRNA (small interfering RNA) proved that p38α MAPK/ATF-2 and JNK1/c-Jun pathways were responsible for caffeine-evoked Fas/FasL up-regulation. Moreover, Ca2+ and ROS (reactive oxygen species) were demonstrated to be responsible for ASK1 activation and Akt/ERK inactivation respectively in caffeine- and caffeine/adaphostin-treated cells. Likewise, adaphostin functionally enhanced caffeine-induced Fas/FasL up-regulation in leukaemia cells that expressed Bcr/Abl. Taken together, the results of the present study suggest a therapeutic strategy in improving the efficacy of adaphostin via Fas-mediated death pathway activation in Bcr/Abl-positive leukaemia.


Leukemia ◽  
2020 ◽  
Vol 34 (10) ◽  
pp. 2824-2825
Author(s):  
Robert Peter Gale ◽  
Hillard M. Lazarus ◽  
Gordon L. Phillips
Keyword(s):  

2017 ◽  
Vol 182 (4) ◽  
pp. 581-583 ◽  
Author(s):  
Thomas Menter ◽  
Boris Kuzmanic ◽  
Christoph Bucher ◽  
Michael Medinger ◽  
Joerg Halter ◽  
...  

1995 ◽  
Vol &NA; (1001) ◽  
pp. 5
Author(s):  
&NA;
Keyword(s):  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Valerie Barbier ◽  
Johanna Erbani ◽  
Corrine Fiveash ◽  
Julie M. Davies ◽  
Joshua Tay ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 16528-16528
Author(s):  
G. Biaggi ◽  
A. Santagostino ◽  
D. Manachino ◽  
T. Posca ◽  
G. Forti ◽  
...  

16528 Background: Intensive Induction Treatment (IIT) increases chances of longer survival in acute myeloid leukaemia (AML). Our aim was to improve outcome and to evaluate safety and tolerability of IIT in very elderly patients (pts). Otherwise they have a median surviving time of 11 weeks without treatment. Methods: From October 2003 to November 2005 we treated 23 pts, 16 Males (M) and 7 Female (F); median age 75.5 years (range 68–95). According FAB classification they were 1 M0, 10 M1, 5 M2, 6 M4, 1 M5. ECOG performance status (PS) was 0 in 6 pts, 1 in 5 pts, 2 in 7 pts and 3 in 5 pts. All pts underwent IIT with different schedules: only a female 95 years old had less intensive treatment. Immune-chemotherapy was also admitted. Schedules were: 3+7 IDA+ARA-C in 8 pts; MY-FLAI in 7 pts; VP+ARA-C 1 = ≥ 5 in 2 pts; IDA+ARA-C 1 = ≥ 2 in 4 pts; ARA-C + 6TG in 1 pt. Eleven pts underwent second line treatment. Results: Five pts are alive and 18 dead. We obtained 7 complete responses (CR) (32%) and 1 partial response (PR) (RR 36%);. The median CR duration was 7.5 months (range 1–12).Throughout IIT we observed 5 toxic deaths (23%) because of infections and 2 deaths not leukaemia therapy related (heart failure). The median Overall Survival (OS) was 9 months. Conclusions: Despite the toxic deaths due to the treatment, we obtained in 32% of the pts CR longer compared to palliative or best supportive care; also the median OS was longer than we can expected without chemotherapy. Our data support in our opinion the feasibility and the utility of an IIT in very elderly patients with good PS. No significant financial relationships to disclose.


2002 ◽  
Vol 116 (1) ◽  
pp. 57-77 ◽  
Author(s):  
Farhad Ravandi ◽  
Moshe Talpaz ◽  
Hagop Kantarjian ◽  
Zeev Estrov

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