Zinc finger protein 384 (ZNF384) impact on childhood mixed phenotype acute leukemia and B-cell precursor acute lymphoblastic leukemia.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous malignancy and consists of several genetic abnormalities. Some of these abnormalities are used in clinics for risk calculation and treatment decisions. Patients with ZNF384 rearrangements had a distinct expression profile regardless of their diagnosis, BCP-ALL or mixed phenotype acute leukemia (MPAL) and defined as a new subtype of ALL. In this study, we screened 42 MPAL and 91 BCP-ALL patients for the most common ZNF384 fusions; ZNF384::TCF3, ZNF384::EP300 and ZNF384::TAF15 by using PCR. We identified ZNF384 fusions in 9.5% of MPAL and 7.6% of BCP-ALL. A novel breakpoint was identified in ZNF384::TCF3 fusion in one BCP-ALL patient. T-myeloid MPAL patients showed significantly lower ZNF384 expression compared to lymphoid groups. Patients with ZNF384r had intermediate survival rates based on other subtypes. Prognostic and patient-specific treatment evaluation of ZNF384 fusions in both ALL and MPAL might help to improve risk characterization of patients.

The Development of Chylothorax in a Child With T-cell Lymphoblastic Lymphoma and Ataxia Telangiectasia During Induction Therapy.

Chylothorax is an unusual complication of childhood cancer. It causes to additional morbidity and mortality during management. It should be kept in mind that chylothorax may occur due to mass shrinkage during treatment in patients with mediastinal mass and ductus thoracicus invasion at the initial diagnosis and necessary measures should be taken. This case was presented because of the rarity in pediatric oncology practice.

Successful treatment of multiple relapsed-refractory Langerhans cell histiocytosis with cyclosporine.

Langerhans cell histiocytosis is a rare hematologic disorder and patients who fail first-line treatment have a poor prognosis, and require more intensive treatment. We present an infant diagnosed with multisystem Langerhans cell histiocytosis refractory to multimodal therapy who was successfully treated with cyclosporine. Cyclosporine might be an effective alternative drug as nonmyelosuppressive rescue therapy for multiple relapsed-refractory Langerhans cell histiocytosis that has not achieved remission with cladribine and cytarabine therapy.

A Case With Pyruvate Kinase Deficiency Remarkably Sensitive to Heat.

Pyruvate kinase (PK) deficiency is the most common defect of the glycolytic pathway leading to congenital hemolytic anemia. We present the case of an 18-year-old boy with chronic nonspherocytic hemolytic anemia, who had remarkable sensitivity to heat. Moreover, the patient showed clinical impairment in the last year. For this reason, we excluded the immunologic or infectious nature (malaria, babesia), which may play a role in the worsening of anemia. Red blood cell enzyme assay showed the presence of a significant increase in other enzyme activities, except for PK, suggesting a PK deficiency in the patient. The molecular analysis of the PK-LR gene revealed the presence of a novel homozygote missense mutation (c.581G>C, p.Arg194Pro). The mutant enzyme displayed heat instability. In addition, we analyzed bilirubin uridine diphosphate (UDP)-glucuronosyltransferase 1A1 gene that revealed a heterozygous state ([TA]6/[TA]7). After a clear diagnosis of PK deficiency, the patient underwent splenectomy.

Assessment of tumors in children with tuberous sclerosis: a single centre's experience.

AIM: As a result of mutations in TSC1 (9q34) and TSC2 (16p13.3) tumor supressor genes, the mammalian target of the rapamycin (mTor) signaling pathway is overactivated in patients with tuberous sclerosis. Abnormal cell proliferation and differentiation is responsible for the growth several different tumors. The aim of this study was to review tumors in our patients with tuberous sclerosis. MATERIAL AND METHODS: Thirty-six patients with tuberous sclerosis were reviewed retrospectively in terms of age, sex, family history, clinical findings, presence of tumors, and treatments. RESULTS: Our study included 36 patients (18/18:M/F) aged between two days and 17 years with a median age of 6 years. There were hypopigmented spots in 30 patients, seizures in 28 patients, and a family history in 11 patients. Tumors related to tuberous sclerosis were renal angiomyolipomas in 21 patients, cardiac rhabdomyomas in 11, subependymal giant cell astrocytomas in seven, and non renal hamartoma in one patient. Everolimus treatment was used in only two patients because of hemodynamic instability. CONCLUSIONS: Tuberous sclerosis is a multisystemic disease characterized by the presence of various benign tumors and neurologic disorders. Renal angiomyolipomas, cardiac rhabdomyomas, and subependymal giant cell astrocytomas are commonly observed in patients with tuberous sclerosis. mTOR inhibitors such as everolimus and sirolimus have been increasingly used in the treatment of these tumors. However, the duration and optimal dose of mTOR inhibitors is still controversial and should be used in selected cases.

Squamous cell carcinoma associated with Xeroderma pigmentosum: an unusual presentation with a tremendously huge mass over the face and paraneoplastic hypercalcemia-hyperleukocytosis.

Emir S, Hacisalihoglu S, Özyörük D, Kaçar D, Erdem A, Karakus E. Squamous cell carcinoma associated with Xeroderma pigmentosum: an unusual presentation with a tremendously huge mass over the face and paraneoplastic hypercalcemia-hyperleukocytosis. Turk J Pediatr 2017; 59: 711-714. Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that results from genetic defects in DNA repair and manifests with a marked hypersensivity to ultraviolet rays. Children with X-P are at high risk of developing skin cancers. On the other hand, hypercalcemia-hyperleukocytosis is a rare paraneoplastic syndrome in children with cancer compared to adults. Here, we report a five-year-old female with X-P and squamous cell carcinoma (SCC). The patient presented with a necrotic, ulcerating huge mass sized 20x15x10 cm involving the right half of the face. She had a history of increased freckling over the face since the age of two years. Her other cutaneous findings are dryness of skin, photosensitivity, freckling and telengiectasis all over the body. A diagnosis of Xeroderma pigmentosum was made based on clinical features. She also had high fever, anemia, hyperleukocytosis, thrombocytosis and hypercalcemia. After pathological diagnosis of squamous cell carcinoma, she was treated with chemotherapy. All the symptoms and signs resolved dramatically with the initiation of chemotherapy. Our case is an example of early development of massive disfiguring SCC in children with undiagnosed and untreated X-P. Although we could not prove the paraneoplastic nature of hypercalcemia-hyperleukocytosis, dramatic response to the chemotherapy may be an evidence for paraneoplastic origin.

Is kiwifruit allergy a matter in kiwifruit-cultivating regions? A population-based study.

BACKGROUND: Although kiwifruit is known as a common cause of food allergy, population-based studies concerning the prevalence of kiwifruit allergy do not exist. We aimed to determine the prevalence and clinical characteristics of IgE-mediated kiwifruit allergy in 6-18-year-old urban schoolchildren in a region where kiwifruit is widely cultivated. METHODS: This cross-sectional study recruited 20,800 of the randomly selected 6-18-year-old urban schoolchildren from the Rize city in the eastern Black Sea region of Turkey during 2013. Following a self-administered questionnaire completed by the parents and the child, consenting children were invited for skin prick tests (SPTs) and oral food challenges (OFCs). Children with suspected IgE-mediated kiwifruit were skin prick tested with kiwifruit (commercial allergen and prick-to-prick test with fresh kiwifruit) and a pre-defined panel of allergens (banana, avocado, latex, sesame seed, birch, timothy, hazel, cat, Dermatophagoides pteronyssinus, and Dermatophagoides farinae). All children with a positive SPT to kiwifruit were invited for an open OFC. The prevalence of IgE-mediated kiwifruit allergy was established using open OFCs. RESULTS: The response rate to the questionnaire was 75.9% (15783/20800). The estimated prevalence of parental-perceived IgE-mediated kiwifruit allergy was 0.5% (72/15783) (95% CI, 0.39-0.61%). Of the 72 children, 52 (72.2%) were skin tested, and 17 (32.7%) were found to be positive to kiwifruit with both commercial extract and kiwifruit. The most frequently reported symptoms in kiwifruit SPT-positive children were cutaneous (n = 10, 58.8%) followed by gastrointestinal (n = 6, 35.3%) and bronchial (n = 4, 23.5%). Oral symptoms were reported in six (35.3%) children. All children who were kiwifruit positive by SPT were found positive during the oral challenge. The confirmed prevalence of IgE-mediated kiwifruit allergy by means of open OFC in 6-18-year-old urban schoolchildren living in Rize city was 0.10% (95% CI, 0.06-0.16). CONCLUSION: Prevalence of parental-perceived and clinically confirmed kiwifruit allergy is not consistent. In contrast to expectations, kiwifruit allergy prevalence was low in a city where it is cultivated and highly consumed.

Prevalence and genotype distribution of rotaviruses in children with gastroenteritis in Rize province.

Determination of the distribution of rotavirus genotypes is essential for understanding the epidemiology of this virus responsible for nearly half a million of deaths in patients with gastroenteritis worldwide. In the present study, we aimed to genotype the rotavirus strains isolated from diarrheal stool samples in children under 5 years old. A total of 1297 fecal samples were collected, and rotavirus antigen was detected in 73 of these samples. Antigen-positive samples were transferred to the Public Health Agency of Turkey, Molecular Microbiology Research Laboratory, and were tested for determination of genotypes G and P using semi-nested multiplex polymerase chain reaction method performed with consensus- and genotype-specific primers. Twelve specimens were found to be negative for rotavirus in genotyping method. All the positive-strains were in G1-4, G8-9, P(4), P(8), and P(9) genotypes. The most frequent GP genotype combinations were found to be G9P(8) in 21 strains (34.4%), G2P(4) in 14 strains (23.0%), and G1P(8) in 12 strains (19.7%). We found 10 distinct genotypes amongst a total of 61 strains. Among the strains isolated and genotyped in our study, 90.2% (55/61) and 67.2% (41/61) have already been included in the two existing commercial vaccines. In conclusion, these findings implicate the necessity of development of region-specific vaccines after evaluation of the local genotype distribution. Further studies on the large number of rotavirus strains would contribute to this process.

In vitro determination of the apoptotic effect of heparin on lymphoblasts using DNA analysis and measurements of Fas and Bcl-2 proteins by flow cytometry.

Heparin has an apoptotic effect beside its anticoagulant, anti-inflammatory, antihypertensive, and antiproliferative effects. In this study, the authors detected the percentages of apoptotic lymphoblasts and the expressions of apoptotic Fas protein and antiapoptotic Bcl-2 protein with flow cytometry in vitro after the incubation of lymphoblasts with heparin. Eleven newly diagnosed acute lymphoblastic leukemia (ALL) children were included in the study. Lymphoblasts were incubated in all different levels of heparin concentrations (0, 10, and 20 U/mL) and the percentages of apoptotic lymphoblasts and the percentages of Fas protein and Bcl-2 proteins were simultaneously measured by flow cytometry at 0, 1, and 2 h. At 0, 1, and 2 h, apoptosis was determined when heparin was added in 10- and 20-U/mL concentrations (p <.05). The apoptotic effect of heparin on lymphoblasts was higher at the first hour than at 0 and 2 h in 10- and 20-U/mL heparin concentrations (p <.01). The highest apoptosis was detected in the 20-U/mL heparin concentration at the first hour. The expression levels of Fas protein on lymphoblasts were higher at the first hour than at 0 and 2 h in 10- and 20-U/mL heparin concentrations (p <.001). The highest expression of Fas protein was observed in the 20-U/mL heparin concentration at the first hour. The expression levels of Bcl-2 protein on lymphoblasts were lower at the first hour than at 0 and 2 h in 10- and 20-U/mL heparin concentrations (p <.001). The lowest expression of Bcl-2 protein was detected in the 20-U/mL heparin concentration at the first hour. Increased concentrations of heparin had an increasing effect on the percentages of apoptotic lymphoblasts. The expression percentages of Fas protein on lymphoblasts also increased, whereas the expression percentages of Bcl-2 protein on lymphoblasts decreased (p <.05). These results suggest that low-dose heparin may cause significant apoptosis of lymphoblasts in newly diagnosed ALL patients.

Treatment of dyskeratosis congenita with granulocyte-macrophage colony-stimulating factor and erythropoietin.

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by reticulate skin pigmentation, nail dystrophy, mucosal leucoplakia, and bone marrow failure. Pancytopenia is difficult to manage in patients with this disorder. We describe a 13-month-old-boy who presented with reticulate skin lesions, paleness, and hepatosplenomegaly. Anemia and leukopenia developed by the age of 43 months. The patient was treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) (5 microg/kg/d, subcutaneously) for 19 months and erythropoietin (150 U/kg 3 days in a week, subcutaneously) for 8 months, with excellent neutrophil and hemoglobin response. Recurrent infections were not developed after starting GM-CSF, and packed red blood cell transfusion was not given to the patient after starting erythropoietin. GM-CSF combined with erythropoietin may be used in the treatment of bone marrow failure in patients with DC without an HLA-identical donor.