Article
Relapsed acute lymphoblastic leukemia-specific mutations in NT5C2 cluster into hotspots driving intersubunit stimulation.
Leukemia - 1 Jun 2018
Hnízda Aleš, Fábry Milan, Moriyama Takaya, Pachl Petr, Kugler Michael, Brinsa Vítězslav, Ascher David B, Carroll William L, Novák Petr, Žaliová Markéta, Trka Jan, Řezáčová Pavlína, Yang Jun J, Veverka Václav
Abstract excerpt
Activating mutations in NT5C2, a gene encoding cytosolic purine 5'-nucleotidase (cN-II), confer chemoresistance in relapsed acute lymphoblastic leukemia. Here we show that all mutants became independent of allosteric effects of ATP and thus constitutively active. Structural mapping of mutations described in patients demonstrates that 90% of leukemia-specific allelles directly affect two regulatory hotspots within...
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