Ömer Doğru

Prognostic significance of NOTCH1 and FBXW7 mutations in pediatric T-ALL.

The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T- or B-lymphocyte lineage commitment. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1 pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activating NOTCH1 mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients. NOTCH1 and FBXW7, NOTCH1 alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However, NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.

Acute promyelocytic leukemia treated with idarubicin complicated by focal segmental glomerulosclerosis.

The authors report a 9-year-old boy presenting with a left cerebral ischemic infarction as the first manifestation of acute promyelocytic leukemia. During consolidation chemotherapy, the patient developed nephrotic syndrome and a renal biopsy revealed focal segmental glomerulosclerosis (FSGS). Remission in bone marrow was achieved with chemotherapy, however, new intracranial ischemic areas developed on follow-up. Acute promyelocytic leukemia complicated by FSGS has not been previously reported in children. There may be a relationship between anthracycline treatment and FSGS. Thrombosis could be related with both leukemia and nephrotic syndrome, here thrombosis was the initial symptom, before FSGS was diagnosed.

A Possible Role for WNT5A Hypermethylation in Pediatric Acute Lymphoblastic Leukemia.

Objective: 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. Materials and 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. 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.

A pediatric renal lymphoma case presenting with central nervous system findings.

In pediatric patients renal lymphoma frequently presents in the form of multiple, bilateral mass lesions, infrequently as a single or retroperitoneal mass, and rarely as diffuse infiltrative lesions. In patients with apparent central nervous system involvement close attention to other physical and laboratory findings are essential for preventing a delay in the final diagnosis. Herein we present a pediatric patient with renal lymphoma that presented with central nervous system findings that caused a delay in diagnosis. Conflict of interest:None declared.

Treatment of pediatric Burkitt lymphoma in Turkey.

This study aimed to assess the demographic data and treatment results of children who were diagnosed with Burkitt lymphoma and treated according to the Berlin-Frankfurt-Münster-95 (BFM) protocol in a single institution. A total of 48 patients (37 boys, 77%) with a median age of 8 years (range 2 to 16 years) at diagnosis, were evaluated. Primary tumor sites were abdomen (70.8%), head and neck (22.9%), peripheral lymph node (2%), bone (2%), and testis (2%). The 5-year overall survival (OS) and event-free survival (EFS) were 78.1±4% and 76.6±6%, respectively. In univariate analysis, hemoglobin level less than 10 g/dL, cerebrospinal fluid (CSF) positivity and dialysis requirement at diagnosis were found to be important reverse predictor factors for EFS (P; 0.001, 0.001, 0.004, respectively). In multivariate analysis, hemoglobin level less than 10 g/dL and dialysis at diagnosis were found to be important reverse predictor factors for EFS (P; 0.0001). The EFS of our patients was lower than the values achieved with BFM-95 protocol in other centers. This study provides evidence that low hemoglobin level, CSF positivity and dialysis at diagnosis were important predictor factors for EFS in children with Burkitt lymphoma.

Yalancı trombositopeni Olgu Sunumu

Nowadays automated blood cell analysis is being widely used When the history and physical examination do not suggest a defect in hemostasis the thrombocyte count is found low in blood with the anticogulants EDTA or citrate although a blood film prepared directly from blood optained by finger puncture reveales normal thrombocytes This thrombocytopenia is called pseudo or spurious thrombocytopenia Here sharing our experience on a pseudothromboctopenic child we want to point to this topic altough it is less common in pediatric patients than adults Turk Arch Ped 2009; 44: 73 4 Key words: Childhood spurious thrombocytopenia thrombocytopenia

Çocukluk çağı Hodgkin hastalığının seyri ile hematolojik ve diğer değişkenlerin ilişkisi Orijinal Araştırma

Aim: Hodgkin’s disease HD is a common malignancy in children and is curable in over 90 of cases At diagnosis prediction of the outcome is important to avoid overtreating some patients and identifying others who need more intensified chemotherapy In this study our aim is to determine the prognosis among relapsed deceased and patients who are in remission according to erythrocyte sedimentation rate ESR hemoglobin leukocyte and lymphocyte levels that were taken at the time of diagnosis Material and Method: There were 170 patients diagnosed as HD admitted to Cerrahpasa Faculty of Medicine Pediatric Hematology and Oncology Department during 1975 2006 The records were reviewed retrospectively Clinical evaluation and staging was performed in all patients Disease staging was done according to Ann Arbor classification system and histopathological subtypes were defined using Rye criteria One hundred twenty six patients were eligible out of 170 Results: The mean age was 8 6 2 3 years and male female ratio was 2 2 87 males 70 and 39 females 30 Staging was as follows: stage I; 3 2 ; stage II 83 66 ; stage III 24 19 ; stage IV 16 13 The most common histological subtype was mixed cellular MC: 69 55 followed by nodular sclerosis NS:35 28 lymphocyte predominance LP: 7 5 and lymphocyte depletion LD: 3 2 with 12 unkown histology 9 The mean hemoglobin Hb levels were 10 7±2 17 gr dl 4 5 13 5 Hb levels less than 10 5 gr dl were found in 29 23 Mean leukocyte count were 7550±2170 mm3 2100 21600 mm3 while leukocytosis gt; 15 000 mm3 and lymphoctopenia a lymphocyte count of less than 600 mm3 were rare respectively; 7 5 1 0 7 Mean ESR of the group was found 55 53±38 6 mm hour median: 47 range:1 160 The ESR values of relapsed expired or patients in remission were 52 4±31mm h 54 5±2mm h and 53 8±3mm h respectively Relapse occurred in 12 9 5 ; 11 died 8 7 ; and 103 patients 81 7 were in remission There was no difference between relapsed dead or remission patients for any hematological parameters Conclusion: It is found that hematological parameters in HD which were investigated to predict prognosis were not worthy in pediatric patients unlike adult patients B sympotms and histological subtypes had no impaction prognosis while treatment regiment were associated with overal survi Turk Arch Ped 2008; 43: 46 9 Key words: Childhood hematological parameters Hodgkin disease prognostic values

Çocuk acil servisinde kanama nedenleri Orijinal Araştırma

Amac: Damar duvarinda zedelenme sonucunda kan akiminin engellenemedigi, kanamanin durdurulamadigi ve damar butunlugunun saglanamadigidurumlarda kanama olusur. Anormal kanama edinsel ya da kalitsal olarak pihtilasma faktorleri, trombosit veya damar duvar hastaliklarisonucunda gelisebilir. Kanama genellikle aileleri korkutan bir acile basvuru nedenidir.Gerec-Yontem: Bu calismada Ocak 1998- Ocak 2003 tarihleri arasinda Cerrahpasa Tip Fakultesi Cocuk acil birimine kanama nedeni ilebasvuran 78 olgu etiolojik olarak degerlendirildi ve sunuldu.Bulgular: Kanama olarak en sik hematuri dikkat cekti (20/78 ; %26). Olgularin %30’unda etiolojik neden idrar yolu enfeksiyonu idi. Sindirim sistemi kaynaklikanama olarak melena, hematemez, hematosezi toplam 20 (%26) olguda saptandi. Akut gastroenterit ozellikle hematosezi nedeni olarak %33 oranindasaptanirken; melena ve hematemez etiolojisinde ise gastrit, ulser ve ust sindirim sistemi kanamalari onemli yer tutmakta idi. Epistaksis ucuncu sikliklarastlanilan bir bulgu idi (18/78; % 23). Ust solunum yolu enfeksiyonu en sik epistaksis nedeni olarak bulundu ( % 60). Cilt kanamalari (petesi 10/78; ekimoz4/78) %18 oraninda saptandi. Etiolojisinde % 80 idiyopatik trombositopenik purpura vardi. Ancak % 10 olguda malinite ve %50 olguda travma etioloji nedeniidi. Yumusak doku, hemartroz ve mukozal kanamalarin nedeni ise genellikle kanama diyatezi idi. Kanama nedeni ile hasta kaybedilmedi.Cikarimlar: Kanama acil tetkik ve tedavisi gereken bir durumdur. En sik saptanan nedenler goz onunde tutularak gereksiz pahali tetkik vegirisimlerden kacinarak iyi oyku ve klinik verilerle kisa surede sonuca ulasilabilir.Bu calismada Cocuk Acil birimine kanama nedeni ilebasvuran olgular etiolojik olarak degerlendirilmis vesunulmak istenmistir.Gerec ve YontemOcak 98- Ocak 2003 dort yillik donemde Cerrahpasa TipFakultesi Cocuk Acil poliklinigimize bas vuran 37 059cocuk geriye donuk olarak dosyalarindan degerlendirildi.Bunlardan 78 (% 0,2) olgunun acile basvuru nedeni sadecekanama idi. Olgularin 30’u kiz , 48’i erkekti. Olgular, yasve kanama bolgesine gore gruplandirilarak altta yatan neden