FRANKFURT. Acute
lymphoblastic leukaemia (ALL) is the most common kind of cancer in children.
T-ALL, a subtype that resembles T-lymphocytes, can be treated successfully with
the drug nelarabine. The drug has not been successful, however, with B-ALL, a
subtype resembling B-lymphocytes. Since the 1980s, oncologists have been puzzled
as to the cause of this difference. Now, an international research team headed
by 51猎奇 and the University of Kent has discovered the reason:
B-ALL cells contain the enzyme SAMHD1, which deactivates the drug.
In the current issue of 鈥淐ommunications
Biology", Professor Jindrich Cinatl from the Institute for Medical Virology at
51猎奇 and Professor Martin Michaelis from the School of Biosciences
at the University of Kent report on their investigations with nelarabine on
different cell lines. 鈥淣elarabine is the precursor of the drug, a prodrug, that
does not become effective until it is combined with three phosphate groups in
the leukaemia cell," explains Professor Cinatl. 鈥淚n studies of various ALL cell
lines and leukaemia cells from ALL patients, we have been able to demonstrate
that the enzyme SAMHD1 splits the phosphate groups off so that the medicine loses
its effect." Because B-ALL cells contain more SAMHD1 than T-ALL cells,
nelarabine is less effective with B-ALL.
These results could improve the treatment
of ALL in the future. In rare cases, B-ALL cells contain very little SAMHD1 so
that treatment with nelarabine would be possible. On the contrary, there are
also rare cases of T-ALL exhibiting a lot of SAMHD1. In such cases, the
otherwise effective nelarabine would not be the right medication. Professor
Michaelis observes: 鈥淪AMHD1 is thus a biomarker that allows us to better adapt
treatment with nelarabine to the individual situation of ALL patients."
Tamara Rothenburger, whose doctoral
dissertation was funded by the association 鈥淗ilfe f眉r krebskranke Kinder
Frankfurt e.V鈥�, is satisfied when she looks back at her research. 鈥淚 hope that
many children with leukaemia will benefit from the results." The research was
also supported by the Frankfurt Stiftung f眉r krebskranke Kinder. Additional
members of the research group are Ludwig-Maximilians-Universit盲t Munich, and
University College London.
Publication:
Tamara Rothenburger, Katie-May McLaughlin,
Tobias Herold, Constanze Schneider, Thomas Oellerich, Florian Rothweiler,
Andrew Feber, Tim R. Fenton, Mark N. Wass, Oliver T. Keppler, Martin Michaelis,
Jindrich Cinatl. SAMHD1 is a key
regulator of the lineage-specific response of acute lymphoblastic leukaemias to
nelarabine, in: Communications Biology, DOI
10.1038/s42003-020-1052-8,
Further
information:
Prof. Dr. rer. nat. Jindrich Cinatl
Institute for Medical Virology
University Hospital Frankfurt
Tel.: +49 69 6301-6409
E-mail: cinatl@em.uni-frankfurt.de
