Core binding factor (CBF)-positive acute myeloid leukemia (AML) presents a favorable prognosis, except for patients with KIT mutation, especially D816 mutation. The current retrospective study attempted to validate a prognostic role of KIT mutation in 121 Korean patients with CBF AML. The study patients consisted of 121 patients with CBF AML (82 patients with RUNX1/RUNX1T1 [67.8 %] and 39 patients with CBFB/MYH11 [32.2 %]) recruited from eight institutions in Korea. All patients received idarubicin plus cytarabine or behenoyl cytosine arabinoside 3 + 7 induction chemotherapy. The KIT gene mutation status was determined by direct sequencing analyses. A KIT mutation was detected in 32 cases (26.4 %) in our series of patients. The KIT mutation was most frequent in exon 17 (n = 18, 14.9 %; n = 16 with D816 mutation), followed by exon 8 (n = 10, 8.3 %). The presence of KIT D816 mutation was associated with adverse outcomes for the event-free survival (p = 0.03) and for the overall survival (p = 0.02). The unfavorable impact of D816 mutation was more prominent when the analysis was confined to the RUNX1/RUNX1T1 subtype. The KIT mutation was detected in 26.4 % of Korean patients with CBF AML. The KIT D816 mutation demonstrated an unfavorable prognostic implication, particularly in the RUNX1/RUNX1T1 subtype.

© F e r r a t a S t o r t i F o u n d a t i o nIn this regard, we investigated the molecular genetic defects of natural anticoagulant deficiencies (PC, PS, and AT) in a large number of consecutive VTE patients and in the general population in Korea screened by coagulation tests. The results revealed unique frequencies and mutation spectrums of natural anticoagulant deficiencies in the group of VTE patients and in the general population. These frequencies and the mutation spectrums in Korea were not only distinct from those in Caucasian populations but also from those in other Asian countries. Methods Patients and populationThe group of patients consisted of consecutive VTE patients screened for thrombophilia including PC, PS, and AT deficiencies at Samsung Medical Center, Seoul, Korea, from January 2005 to December 2012. For the population group, at least 3,000 individuals visiting the institution for routine check-ups were screened from September 2005 to January 2006 using the same coagulation tests for natural anticoagulant deficiency as those used in the patients. In each group, those suspected of having a natural anticoagulant deficiency underwent molecular genetic tests to confirm the deficiency. In both groups, we excluded those with low levels of multiple (2 or more) natural anticoagulants, especially in association with underlying liver disease or other extrinsic factors. Written informed consent was obtained from the patients in the study, which was approved by the Institutional Review Board of the Samsung Medical Center, Seoul, Korea. Coagulation testsThe thrombophilia profile tests for VTE patients included screening for genetic thrombophilia: PC activity (Stachrom ® Protein C, Diagnostica Stago, Asnieres-Sur-Seine, France), PS free antigen (Liatest ® Free Protein S, Diagnostica Stago), and AT activity (Stachrom ® ATIII, Diagnostica Stago). All coagulation tests were performed on the STA ® coagulation analyzer (Diagnostica Stago). The local reference intervals were determined according to the guidelines from the Clinical and Laboratory Standards Institute (http://www.clsi.org/) as the 2.5-97.5 percentiles (PC activity, PS free antigen,.2% for males and 56.0-132.6% for females; and AT activity, 81.5-119.3%). 10 Tests for PC antigen, PS total antigen and activity, and AT antigen were additionally performed when indicated. Natural anticoagulant deficiency was suspected in VTE patients when the result was below the lower limit of the reference interval (2.5 percentile). Screening for natural anticoagulant deficiency in the population group was performed using the same coagulation tests as those used in the VTE patients. Individuals with levels of PC, PS, or AT below the 1 st percentile were selected for molecular genetic tests. Molecular genetic analysesGenomic DNA was extracted from peripheral blood leukocytes using the Wizard Genomic DNA Purification kit following the standard protocols (Promega, Madison, WI, USA). Molecular genetic diagnosis of natural anticoagulant deficiency was performed by...

Familial hemophagocytic lymphohistiocytosis (familial HLH or FHL) is a potentially fatal autosomal recessive disorder. Our previous study demonstrated that UNC13D mutations (FHL3) account for ~90 % of FHL in Korea with recurrent splicing mutation c.754-1G>C (IVS9-1G>C). Notably, half of the FHL3 patients had a monoallelic mutation of UNC13D. Deep intronic mutations in UNC13D were recently reported in patients of European descent. In this study, we performed targeted mutation analyses for deep intronic mutations and investigated on the founder effect in FHL3 in Korean patients. The study patients were 72 children with HLH including those with FHL3 previously reported to have a monoallelic UNC13D mutation. All patients were recruited from the Korean Registry of Hemophagocytic Lymphohistiocytosis. In addition to conventional sequencing of FHL2-4, targeted tests for c.118-308C>T and large intronic rearrangement mutations of UNC13D were performed. Haplotype analysis was performed for founder effects using polymorphic markers in the FHL3 locus. FHL mutations were detected in 20 patients (28 %). Seventeen patients had UNC13D mutations (FHL3, 85 %) and three had PRF1 mutations (FHL2, 15 %). UNC13D:c.118-308C>T was detected in ten patients, accounting for 38 % of all mutant alleles of UNC13D, followed by c.754-1G>C (26 %). Haplotype analyses revealed significantly shared haplotypes in both c.118-308C>T and c.754-1G>C, indicating the presence of founder effects. The deep intronic mutation UNC13D:c.118-308C>T accounts for the majority of previously missing mutations and is the most frequent mutation in FHL3 in Korea. Founder effects of two recurrent intronic mutations of UNC13D explain the unusual predominance of FHL3 in Korea.

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by pure red cell aplasia, various congenital anomalies, and cancer predisposition. We report a novel mutation in the RPS17 gene in a Korean patient with DBA. The mutation occurred in the translation initiation codon, changing Atg to Gtg (c.1A>G), thus disrupting the natural start of the RPS17 protein biosynthesis. This is the third case of DBA from a RPS17 mutation in the literature and is the second case of a RPS17 mutation in the translation initiation codon, following c.2T>G.