News Release 

Decades old mystery in leukaemia treatment solved

University of Kent

A research team led by the University of Kent and Goethe-University Frankfurt am Main, has solved an almost 40-year old mystery in leukaemia therapy and the drug nelarabine.

Acute lymphoblastic leukaemia (ALL) is the most common cancer in children. There are two types of ALL: B-ALL, which resembles B lymphocytes (B-cells); and T-ALL, which resembles T lymphocytes (T-cells). Since the 1980s, it has been known that the drug nelarabine is effective against T-ALL but not against B-ALL, for reasons unknown.

The new research study now reveals the reason why, and how this can change leukaemia treatments; thanks to the enzyme called SAMHD1.

The research shows that SAMHD1 is present only at low levels in T-ALL, compared to its greater-level of presence in B-ALL cells. Hence, SAMHD1 protects B-ALL cells, but not T-ALL cells, from the anti-cancer effects of nelarabine.

The findings have crucial practical implications. There are rare cases of B-ALL in which leukaemia cells display low SAMHD1 levels and thus may benefit from nelarabine treatment.

Additionally, there are also T-ALL cases in which leukaemia cells have high SAMHD1 levels, which are unlikely to react to nelarabine. Hence, the enzyme SAMHD1 is a biomarker with the potential to tailor nelarabine treatment better to the needs of individual ALL patients.

Dr Mark Wass, an author of the study from the University of Kent, said: 'This work solves an almost 40-year old mystery in leukaemia treatment. The results could immensely impact the effectiveness of particular nelarabine therapy and open other doors of understanding in the effort again this disease.'

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The article 'SAMHD1 is a key regulator of the lineage-specific response of acute lymphoblastic leukaemias to nelarabine' is published in Communications Biology.

Authors:

Tamara Rothenburger, Constanze Schneider, Thomas Oellerich, Jindrich Cinatl - Goethe-University Frankfurt;

Katie-May McLaughlin, Tim Fenton, Mark Wass, Martin Michaelis - School of Biosciences, University of Kent

Tobias Herold, Oliver Keppler - LMU Munich

Andrew Feber - University College London

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