A point mutation in the RNA-binding domain I results in decrease of PKR activation in acute lymphoblastic leukemia

We investigated the presence of mutations in the RBD-I and RBD-II of PKR gene in children with acute lymphoblastic leukemia (ALL). The RNA extracted from bone marrow samples of 15 patients with ALL (5 patients T-lineage; 10 patients B-lineage) was used for to synthesize cDNA and amplify the sequences corresponding to RBD-I and RBD-II. The PCR products were subsequently cloned and sequenced. A point mutation was detected in the RBD-I of PKR from a patient with ALL of T-cell lineage that is located at cDNA nt 50 A → G (17 Tyr→Cys). We also found that activation of a PKR mutant by the polyinosinic acid:polycytidylic acid (poly I:C) is impaired when compared with the wild-type PKR. Additional work is required to elucidate whether this point mutation plays a role in the formation and/or maintenance of leukemic cells. To our knowledge, this study is the first example of detection of a mutation in the RBD-I of PKR gene from tumor cells taken directly from patients.