Acute lymphoblastic leukaemia (ALL) is the\nmost common kind of cancer in children. T-ALL, a subtype that resembles\nT-lymphocytes, can be treated successfully with the drug nelarabine. The drug\nhas not been successful, however, with B-ALL, a subtype resembling\nB-lymphocytes. Since the 1980s, oncologists have been puzzled as to the cause\nof this difference. Now, an international research team headed by Goethe\nUniversity and the University of Kent has discovered the reason: B-ALL cells\ncontain the enzyme SAMHD1, which deactivates the drug.<\/p>\n\n\n\n
In the current issue of \u201cCommunications\nBiology\u201d, Professor Jindrich Cinatl from the Institute for Medical Virology at\nGoethe University and Professor Martin Michaelis from the School of Biosciences\nat the University of Kent report on their investigations with nelarabine on\ndifferent cell lines. \u201cNelarabine is the precursor of the drug, a prodrug, that\ndoes not become effective until it is combined with three phosphate groups in\nthe leukaemia cell,\u201d explains Professor Cinatl. \u201cIn studies of various ALL cell\nlines and leukaemia cells from ALL patients, we have been able to demonstrate\nthat the enzyme SAMHD1 splits the phosphate groups off so that the medicine loses\nits effect.\u201d Because B-ALL cells contain more SAMHD1 than T-ALL cells,\nnelarabine is less effective with B-ALL.<\/p>\n\n\n\n
These results could improve the treatment\nof ALL in the future. In rare cases, B-ALL cells contain very little SAMHD1 so\nthat treatment with nelarabine would be possible. On the contrary, there are\nalso rare cases of T-ALL exhibiting a lot of SAMHD1. In such cases, the\notherwise effective nelarabine would not be the right medication. Professor\nMichaelis observes: \u201cSAMHD1 is thus a biomarker that allows us to better adapt\ntreatment with nelarabine to the individual situation of ALL patients.\u201d<\/p>\n\n\n\n
Tamara Rothenburger, whose doctoral\ndissertation was funded by the association \u201cHilfe f\u00fcr krebskranke Kinder\nFrankfurt e.V\u201c, is satisfied when she looks back at her research. \u201cI hope that\nmany children with leukaemia will benefit from the results.\u201d The research was\nalso supported by the Frankfurt Stiftung f\u00fcr krebskranke Kinder. Additional\nmembers of the research group are Ludwig-Maximilians-Universit\u00e4t Munich, and\nUniversity College London.<\/p>\n\n\n\n