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Hereditary factor X (FX) deficiency is a rare bleeding disorder more prevalent in countries with high rates of consanguineous marriage. In a prospective, open-label, multicenter phase 3 study, 25 IU/kg plasmaderived factor X (pdFX) was administered as on-demand treatment or short-term prophylaxis for 6 months to 2 years. In Turkish subjects (n=6), 60.7% of bleeds were minor. A mean of 1.03 infusions were used to treat each bleed, and mean total dose per bleed was 25.38 IU/kg. Turkish subjects rated pdFX efficacy as excellent or good for all 84 assessable bleeds; investigators judged overall pdFX efficacy to be excellent or good for all subjects. Turkish subjects had 51 adverse events; 96% with known severity were mild/moderate, and 1 (infusionsite pain) was possibly pdFX-related. These results demonstrate that 25 IU/kg pdFX is safe and effective in this Turkish cohort (ClinicalTrials.gov identifier: NCT00930176).

INTRODUCTION: Alpha thalassemia syndromes are caused by mutations on one or more of the four α-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2) cause α+-thalassemia, some cause (-20.5, MED, THAI, FIL) α0 -thalassemia. The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations. METHODS: Two hundred six patients with hypochromic microcytic anemia were evaluated for alpha thalassemia. A venous blood sample of 2 mL was drawn from each patient for DNA isolation. The samples were investigated for α-thalassemia mutations by using the Vienna Lab α-Globlin StripAssay TM commercial kit. RESULTS: Fourteen different mutations were determined in 95 (46.1%) patients. The most common mutation was the 3.7 single gene deletion and was found in 37 patients (n=37/95, 39%). Others common mutations were the 20.5 kb double gene deletion (n=20 patients, 21%), MED double gene deletion (n=17 patients, 17.9%), α2 IVS1 (n=10 patients, 10.5%), α2 cd142 Hb Koya Dora (n=6 patients, 6.3%), α2 polyA1 (Saudi type) (n=6 patients, 6.3%), 4.2 single gene deletion (n=4 patients, 4.2%), α1 cd14 (n=2 patients, 2.1%), and -FIL mutation (n=2 patients 2.1%), respectively. Hb Adana, Hb Icaria, α2 init cd and α2 polyA2 (Turkish type) were found in 1% of the patients (n=1). Seven patients (7.4%) had α-thalassemia triplication. In our study, three mutations (Hb Icaria, α1 cd14, α2 init.cd) were determined firstly in Turkey. Seven mutations (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paksé) were not determined in this study. DISCUSSION AND CONCLUSION: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and β-thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a national database with all mutations in Turkey should be created to screen the alpha thalassemia cost-effectively.

INTRODUCTION: WNT5A is one of the most studied noncanonical WNT ligands and is shown to be deregulated in different tumor types. Our aim was to clarify whether hypermethylation might be the cause of low WNT5A mRNA levels and whether we could restore this downregulation by reversing the event. METHODS: The expression of WNT5A mRNA was studied in a large acute lymphoblastic leukemia (ALL) patient group (n=86) by quantitative real-time PCR. The methylation status was detected by methylation-specific PCR (MSPCR) and bisulphate sequencing. In order to determine whether methylation has a direct effect on WNT5A expression, disease-representative cell lines were treated by 5'-aza-20-deoxycytidine. RESULTS: Here we designed a validation experiment of the WNT5A gene, which was previously examined and found to be differentially expressed by microarray study in 31 T-cell ALL patients. The expression levels were confirmed by quantitative real-time PCR and the expression levels were significantly lower in T-cell ALL patients than in control thymic subsets (p=0.007). MSPCR revealed that 86% of the patients were hypermethylated in the WNT5A promoter region. Jurkat and RPMI cell lines were treated with 5'-aza-20-deoxycytidine and WNT5A mRNA expression was restored after treatment. DISCUSSION AND CONCLUSION: According to our results, WNT5A hypermethylation does occur in ALL patients and it has a direct effect on mRNA expression. Our findings show that epigenetic changes of WNT signaling can play a role in ALL pathogenesis and reversing methylation might be useful as a possible treatment of leukemia.

OBJECTIVE: T-cell acute lymphoblastic leukemia (T-ALL) is associated with recurrent chromosomal aberrations and abnormal ectopic gene expression during T-cell development. In order to gain insight into the pathogenesis of T-ALL this study aimed to measure the level of expression of 7 T-cell oncogenes (LMO2, LYL1, TAL1, TLX1, TLX3, BMI1, and CALM-AF10) in pediatric T-ALL patients. METHODS: LMO2, LYL1, TLX1, TLX3, BMI1, TAL1, and CALM-AF10 expression was measured using quantitative real-time PCR in 43 pediatric T-ALL patients. RESULTS: A high level of expression of LMO2, LYL1, TAL1, and BMI1 genes was observed in a large group of T-ALL. Several gene expression signatures indicative of leukemic arrest at specific stages of normal thymocyte development (LYL1 and LMO2) were highly expressed during the cortical and mature stages of T-cell development. Furthermore, upregulated TAL1 and BMI1 expression was observed in all phenotypic subgroups. In all, 6 of the patients had TLX1 and TLX3 proto-oncogene expression, which does not occur in normal cells, and none of the patients had CALM-AF10 fusion gene transcription. Expression of LYL1 alone and LMO2-LYL1 co-expression were associated with mediastinal involvement; however, high-level oncogene expression was not predictive of outcome in the present pediatric T-ALL patient group, but there was a trend towards a poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 protooncogene expression. CONCLUSION: Poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 proto-oncogene expression indicate the need for extensive study on oncogenic rearrangement and immunophenotypic markers in T-ALL, and their relationship to treatment outcome.

OBJECTIVE: To identify the well-known common translocations and FLT3 mutations in childhood acute myelogenous leukemia (AML) patients in Turkey. METHODS: The study included 50 newly diagnosed patients in which t(15;17), t(8;21), and inv(16) chromosomal translocations were identified using real-time PCR and FLT3 gene mutations were identified via direct PCR amplification PCR-RE analysis. RESULTS: In all, t(15;17) chromosomal aberrations were observed in 4 patients (8.0%), t(8;21) chromosomal aberrations were observed in 12 patients (24.0%), inv(16) chromosomal aberrations were observed in 3 patients (6.0%), and FLT3-ITD mutations were observed in 2 patients (4.0%); FLT3-D835 point mutation heterozygosity was observed in only 1 patient (2.0%) patient. CONCLUSION: Despite of the known literature, our case shows a better survival and this might be due to the complementation effect of the t(15;17) translocation. The lower mutation rate (4%) of FLT3 gene seems to be one of the first results for Turkish population.

OBJECTIVE: We evaluated the clinical findings, laboratory data, management, and outcome of children with rare coagulation deficiencies (RCDs) diagnosed in Turkey during the past 10 years, retrospectively. METHODS: A simple Excel file of questionnaire was sent to contact people in each center to standardize data collection by Turkish Society of Pediatric Hematology, Hemophilia-Thrombosis-Hemostasis subcommittee. RESULTS: Total of 156 patients were included in this study from 12 pediatric referral centers. Most common rare coagulation disorders in the study was as follows: FVII (n: 53, 34%), FV (n: 24, 15.4%), FX (n: 23 case, 14.7%). The most common initial findings in our patients were epistaxis, echymosis and gingival bleeding in all type of RCDs respectively. CONCLUSION: First symptoms are mucosal bleedings and FFP and tranexamic acid is still the most commonly used therapeutic options. We suggest that prophylactic treatment that we use for hemophilia patients should be considered at the very beginning among the therapeutic options for rare factor deficiencies with severe clinical course and factor deficiency that can lead to severe bleeding.