scholarly journals Venetoclax induces rapid elimination of NPM1 mutant measurable residual disease in combination with low‐intensity chemotherapy in acute myeloid leukaemia

2020 ◽  
Author(s):  
Ing S. Tiong ◽  
Richard Dillon ◽  
Adam Ivey ◽  
Tse‐Chieh Teh ◽  
Phillip Nguyen ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Residual Disease ◽  
Low Intensity ◽  
Rapid Elimination ◽  
Measurable Residual Disease ◽  
Acute Myeloid

Measurable residual disease testing in acute myeloid leukaemia

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
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Residual Disease ◽  
Measurable Residual Disease ◽  
Acute Myeloid ◽  
Disease Testing

scholarly journals Measurable residual disease assessment by qPCR in peripheral blood is an informative tool for disease surveillance in childhood acute myeloid leukaemia

2020 ◽  
Vol 190 (2) ◽  
pp. 198-208
Author(s):  
Kristian Løvvik Juul‐Dam ◽  
Hans B. Ommen ◽  
Charlotte G. Nyvold ◽  
Christiane Walter ◽  
Helen Vålerhaugen ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Peripheral Blood ◽  
Disease Surveillance ◽  
Residual Disease ◽  
Disease Assessment ◽  
Measurable Residual Disease ◽  
Acute Myeloid

scholarly journals Pre-clinical activity of combined LSD1 and mTORC1 inhibition in MLL-translocated acute myeloid leukaemia

Leukemia ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 1266-1277 ◽  
Author(s):  
Gauri Deb ◽  
Bettina Wingelhofer ◽  
Fabio M. R. Amaral ◽  
Alba Maiques-Diaz ◽  
John A. Chadwick ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Residual Disease ◽  
Molecular Subtype ◽  
Clinical Activity ◽  
Lineage Differentiation ◽  
A Genome ◽  
Acute Myeloid

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.

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
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
High Frequency ◽  
Residual Disease ◽  
The Body ◽  
Residual Cancer ◽  
Additional Function ◽  
First Remission ◽  
Antigenic Targets ◽  
Acute Myeloid

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.

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