scholarly journals Antigenic Targets for the Immunotherapy of Acute Myeloid Leukaemia

2019 ◽  
Vol 8 (2) ◽  
pp. 134 ◽  
Author(s):  
Ghazala Khan ◽  
Kim Orchard ◽  
Barbara-ann Guinn

One of the most promising approaches to preventing relapse is the stimulation of the body’s own immune system to kill residual cancer cells after conventional therapy has destroyed the bulk of the tumour. In acute myeloid leukaemia (AML), the high frequency with which patients achieve first remission, and the diffuse nature of the disease throughout the periphery, makes immunotherapy particularly appealing following induction and consolidation therapy, using chemotherapy, and where possible stem cell transplantation. Immunotherapy could be used to remove residual disease, including leukaemic stem cells from the farthest recesses of the body, reducing, if not eliminating, the prospect of relapse. The identification of novel antigens that exist at disease presentation and can act as targets for immunotherapy have also proved useful in helping us to gain a better understand of the biology that belies AML. It appears that there is an additional function of leukaemia associated antigens as biomarkers of disease state and survival. Here, we discuss these findings.

Leukemia ◽  
2017 ◽  
Vol 31 (7) ◽  
pp. 1482-1490 ◽  
Author(s):  
C S Hourigan ◽  
R P Gale ◽  
N J Gormley ◽  
G J Ossenkoppele ◽  
R B Walter

2020 ◽  
Vol 190 (2) ◽  
pp. 198-208
Author(s):  
Kristian Løvvik Juul‐Dam ◽  
Hans B. Ommen ◽  
Charlotte G. Nyvold ◽  
Christiane Walter ◽  
Helen Vålerhaugen ◽  
...  

Leukemia ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 1266-1277 ◽  
Author(s):  
Gauri Deb ◽  
Bettina Wingelhofer ◽  
Fabio M. R. Amaral ◽  
Alba Maiques-Diaz ◽  
John A. Chadwick ◽  
...  

AbstractThe histone demethylase lysine-specific demethylase 1 (LSD1 or KDM1A) has emerged as a candidate therapeutic target in acute myeloid leukaemia (AML); tranylcypromine-derivative inhibitors induce loss of clonogenic activity and promote differentiation, in particular in the MLL-translocated molecular subtype of AML. In AML, the use of drugs in combination often delivers superior clinical activity. To identify genes and cellular pathways that collaborate with LSD1 to maintain the leukaemic phenotype, and which could be targeted by combination therapies, we performed a genome-wide CRISPR-Cas9 dropout screen. We identified multiple components of the amino acid sensing arm of mTORC1 signalling—RRAGA, MLST8, WDR24 and LAMTOR2—as cellular sensitizers to LSD1 inhibition. Knockdown of mTORC1 components, or mTORC1 pharmacologic inhibition, in combination with LSD1 inhibition enhanced differentiation in both cell line and primary cell settings, in vitro and in vivo, and substantially reduced the frequency of clonogenic primary human AML cells in a modelled minimal residual disease setting. Synergistic upregulation of a set of transcription factor genes associated with terminal monocytic lineage differentiation was observed. Thus, dual mTORC1 and LSD1 inhibition represents a candidate combination approach for enhanced differentiation in MLL-translocated AML which could be evaluated in early phase clinical trials.


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