Dragana Janic

Publications (17)29.31 Total impact

• Article: Gammopathy and B lymphocyte clonality in patients with Gaucher type I disease.

  Predrag Rodic, Sonja Pavlovic, Tatjana Kostic, Nada Suvajdzic Vukovic, Maja Djordjevic, Zorica Sumarac, Marijana Dajak, Branka Bonaci Nikolic, Dragana Janic
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  ABSTRACT: INTRODUCTION: We evaluated a novel approach for investigation of lymphocyte dysregulation in Gaucher patients by including determination of IgH and TCR gene rearrangements together with levels of immunoglobulins, natural autoantibodies as well as presence of monoclonal protein. MATERIALS AND METHODS: Measurement of serum immunoglobulins, monoclonal immunoglobulins, selected autoantibodies, as well as analysis of immunoglobulin heavy chain and T cell receptor gene rearrangements. RESULTS: Immunoglobulin disorder was detected in 29.6% patients, 40.7% demonstrated presence of B cell clonality and 44.4% demonstrated presence of autoantibodies. In five patients in our series, the presence of IgH gene rearrangement was the only detectable indicator of B cell dysfunction. TCR gene rearrangements were not found in any of the patients. CONCLUSION: Based on our results, we propose IgH gene rearrangements as a new biomarker for investigation of B cell dysfunction occurring as a complication of Gaucher disease.
  Blood Cells Molecules and Diseases 12/2012; · 2.35 Impact Factor
• Article: Colon carcinoma in a child treated with oxaliplatin and antiangiogenic treatment regimens.

  Nada Krstovski, Lidija Dokmanovic, Jelena Lazic, Predrag Rodic, Lejla Paripovic, Dragana Janic
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  ABSTRACT: Colorectal carcinoma is an extremely rare tumor in childhood. Therefore, the role of adjuvant chemotherapy has not been adequately evaluated in children leading to limited data on safety profile and treatment response after application of novel drugs and novel targeted agents. In this report, we describe a case of colon adenocarcinoma in a 13-year-old girl treated with standard adult treatment as well as novel targeted therapy. This case report illustrates initial good disease control with FOLFOX therapy. On the other hand, targeted therapy revealed no improvement in disease control and good safety profile without significant adverse effects.
  Pediatric Hematology and Oncology 07/2012; 29(6):549-50. · 0.89 Impact Factor
• Article: Pediatric non-Hodgkin lymphoma: a retrospective 14-year experience with Berlin-Frankfurt-Münster (BFM) protocols from a tertiary care hospital in Serbia.

  Lidija Dokmanovic, Nada Krstovski, Dragan Vukanic, Dimitrije Brasanac, Predrag Rodic, Mirjana Cvetkovic, Dragana Janic
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  ABSTRACT: Use of current intensive chemotherapy protocols in pediatric non-Hodgkin lymphoma (NHL) in high-income countries resulted in event-free survival (EFS) rates ranging from 80 to 90%. The results are inferior in less privileged countries with limited resources for medical care. There are no reports about comprehensive data analysis in pediatric NHL in Serbia. A retrospective study was carried out at University Children's Hospital, Belgrade, in children aged less than 18 years diagnosed with non-Hodgkin lymphoma from 1997 to 2011. Fifty-seven children were eligible for analysis. Fourteen were diagnosed with lymphoblastic lymphoma, 38 with mature B-cell NHL (B-NHL), and 5 with anaplastic large-cell lymphoma. Mean age at diagnosis was 9.2 years, with male to female ratio 2.35:1. Children were treated according to Berlin-Frankfurt-Münster (BFM) protocols. With median follow-up of 59.3 months, 5-year probability of EFS was 84.1% for all patients, whereas overall survival was 93%. These results with BFM protocol administration, although inferior to leading international groups, reflect good treatment outcome in our patients. To the best of the authors' knowledge, this article presents the first results regarding treatment and survival of childhood NHL in Serbia.
  Pediatric Hematology and Oncology 03/2012; 29(2):109-18. · 0.89 Impact Factor
• Article: 6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner.

  Nikola Kotur, Biljana Stankovic, Katerina Kassela, Marianthi Georgitsi, Anna Vicha, Iliana Leontari, Lidija Dokmanovic, Dragana Janic, Nada Krstovski, Kristel Klaassen, Milena Radmilovic, Maja Stojiljkovic, Gordana Nikcevic, Argiris Simeonidis, Gregory Sivolapenko, Sonja Pavlovic, George P Patrinos, Branka Zukic
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  ABSTRACT: AIM: TPMT activity is characterized by a trimodal distribution, namely low, intermediate and high methylator. TPMT gene promoter contains a variable number of GC-rich tandem repeats (VNTRs), namely A, B and C, ranging from three to nine repeats in length in an A(n)B(m)C architecture. We have previously shown that the VNTR architecture in the TPMT gene promoter affects TPMT gene transcription. MATERIALS, METHODS & RESULTS: Here we demonstrate, using reporter assays, that 6-mercaptopurine (6-MP) treatment results in a VNTR architecture-dependent decrease of TPMT gene transcription, mediated by the binding of newly recruited protein complexes to the TPMT gene promoter, upon 6-MP treatment. We also show that acute lymphoblastic leukemia patients undergoing 6-MP treatment display a VNTR architecture-dependent response to 6-MP. CONCLUSION: These data suggest that the TPMT gene promoter VNTR architecture can be potentially used as a pharmacogenomic marker to predict toxicity due to 6-MP treatment in acute lymphoblastic leukemia patients.
  Pharmacogenomics 02/2012; 13(3):283-95. · 3.97 Impact Factor
• Article: Implementation of a nurse education programme in paediatric oncology using appreciative inquiry: a single center experience in Belgrade, Serbia.

  Jelena Lazic, Magdalena Radenovic, Alison Arnfield, Dragana Janic
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  ABSTRACT: The nursing staff in our center are very committed to the patients but have not had the opportunity for systematic clinical education, since there is no formal education for paediatric hematology and oncology nursing in our country. We joint a project, developed to explore and develop collaborative working between nurses and doctors in paediatric oncology under the auspices of The European Cancer Organization (ECCO), The International Society of Paediatric Oncology (SIOP) and The European Oncology Nursing Society (EONS). The Appreciative Inquiry (AI) approach to change management was chosen as it looks at what works in an organization and builds on that to make improvements. Using AI we chose to develop a programme of education for nursing staff, as a project of local interest, to enhance their skills and knowledge of the specialty with the main aim of providing high quality care and ensuring best practice. We found that collaboration profoundly influenced the working environment and resulted in staff being receptive to new challenges. With improved knowledge, nurses are actually more involved in best practice which, in turn, motivates the doctors and improves professional relationships and the patient's treatment and care. We have stressed the importance of collaborative working throughout and used this model of nurse/doctor collaboration to improve the quality of care in our center. We are very hopeful that this model of collaboration and education will last longer than the project itself and be followed by future generations of doctors and nurses.
  European journal of oncology nursing: the official journal of European Oncology Nursing Society 03/2011; 15(5):524-7. · 1.13 Impact Factor
• Article: Molecular diagnosis of childhood acute leukemia: Serbian experience.

  Aleksandra Drago Krstic, Dragan Micic, Nina Lakic, Marija Guc-Scekic, Dragana Janic
  Pediatric Blood & Cancer 08/2010; 55(2):394-5. · 1.89 Impact Factor
• Article: Functional analysis of the role of the TPMT gene promoter VNTR polymorphism in TPMT gene transcription.

  Branka Zukic, Milena Radmilovic, Maja Stojiljkovic, Natasa Tosic, Farzin Pourfarzad, Lidija Dokmanovic, Dragana Janic, Natasa Colovic, Sjaak Philipsen, George P Patrinos, Sonja Pavlovic
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  ABSTRACT: Thiopurine S-methyltransferase (TPMT) activity is polymorphic, and a trimodal distribution has been demonstrated in Caucasians (low, intermediate and high methylator groups). The TPMT gene promoter contains a variable number of three GC-rich tandem repeats, namely A, B and C, ranging from three to nine in length in a A(n)B(m)C architecture. Here, we investigated the influence of number and type of TPMT gene promoter tandem repeats on human TPMT gene transcription in K562 cells transiently transfected with reporter constructs bearing various variable number of tandem repeats (VNTR) and addressed the interaction of transcription factor binding to the VNTRs by electrophoretic mobility shift assays. We found that the distribution patterns of VNTR alleles do not significantly differ among acute lymphoblastic leukemia patients, acute myeloid leukemia patients and normal individuals. We also demonstrated that the A repeat has a negative effect in TPMT gene transcription and that a positive regulatory element, identified immediately upstream to the VNTR region of the TPMT gene promoter, is indispensable for TPMT gene transcription. Our electrophoretic mobility shift assay analysis indicated that the Sp1 and Sp3 transcription factors bind to the VNTR repeats. Overall, our data underline that both the number and type of VNTRs, as well as the upstream regulatory region of the TPMT gene promoter, determine the overall level of TPMT gene transcription. It remains to be seen whether these VNTRs can be employed as pharmacogenetic markers to individualize thiopurine therapy.
  Pharmacogenomics 04/2010; 11(4):547-57. · 3.97 Impact Factor
• Article: Thalassemia syndromes in Serbia: an update.

  Milena Radmilovic, Branka Zukic, Biljana Stankovic, Teodora Karan-Djurasevic, Maja Stojiljkovic, Vesna Spasovski, Natasa Tosic, Lidija Dokmanovic, Dragana Janic, Sonja Pavlovic
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  ABSTRACT: Thalassemia syndromes constitute a group of genetic disorders, widespread throughout the world. The present study contains data on thalassemia syndromes and their chromosomal environment obtained in Serbia over a period of 10 years. Ten different β-thalassemia (β-thal) mutations and two hemoglobin (Hb) variants were detected in 127 members of 68 families. Hb Lepore-Boston-Washington (Lepore-BW) (δ87Gln-β-IVS-II-8), a thalassemic Hb variant, was shown to be the most common cause of thalassemia in Serbia. Haplotype analyses of the β-globin gene clusters of healthy individuals as well as of individuals affected with β-thal showed that haplotype I was the most frequent haplotype in the Serbian population, followed by haplotypes II and IX. Two novel haplotypes were detected. Haplotype analyses showed the association between certain haplotypes and the most common thalassemic mutations. Results presented in this paper will update the Serbian national mutation database and contribute to a better understanding of genographic history of South European and Balkan populations.
  Hemoglobin 01/2010; 34(5):477-85. · 1.30 Impact Factor
• Article: Incidence of FLT3 and nucleophosmin gene mutations in childhood acute myeloid leukemia: Serbian experience and the review of the literature.

  Nada Krstovski, Natasa Tosic, Dragana Janic, Lidija Dokmanovic, Milos Kuzmanovic, Vesna Spasovski, Sonja Pavlovic
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  ABSTRACT: Mutations in the fms-like tyrosine kinase 3 (FLT3) gene (internal tandem duplication (ITD) and point mutation in the tyrosine kinase domain, FLT3/D835) as well as the nucleophosmin (NPM1) gene are the most common abnormalities in adult acute myeloid leukemia (AML). Their significance in pediatric AML is still unclear. In this study we evaluated the frequency of FLT3 and NPM1 mutations in childhood AML. We also examined clinical features and outcome of these patients. FLT3 and NPM1 mutations were analysed in 42 and 37 childhood AML patients, respectively, using polymerase chain reaction (PCR) and direct sequencing. FLT3 mutations were detected in 4/42 patients (9.5%). The frequencies of FLT3/ITD and FLT3/D835 were the same, 2/42 (4.7%). NMP1 mutations were found in 1/37 patients (2.7%). FLT3 gene mutations were correlated with induction failure. Here we report the results of the study of FLT3 and NPM1 gene mutations in childhood AML patients in Serbia. Low frequencies of these molecular markers point out that these abnormalities are rare in this cohort of patients. Comparative study of data on NPM1 mutations in childhood AML revealed that various NPM1 gene mutation types are associated with childhood AML. Our findings as well as previously reported data, contributes to a hypothesis of different biology and etiology of adult and childhood AML. More extensive studies of NPM1 and FLT3 mutations in childhood AML are needed to determine their biological and clinical importance.
  Medical Oncology 07/2009; 27(3):640-5. · 2.14 Impact Factor
• Article: The use of recombinant activated factor VII during major surgery in a child with Kasabach-Merritt syndrome.

  Dragana Janic, Dimitrije Brasanac, Nada Krstovski, Lidija Dokmanovic, Jelena Lazic, Zoran Krstic
  Pediatric Anesthesia 03/2009; 19(2):177-9. · 2.10 Impact Factor
• Article: Ruptured intramural intestinal hematoma in an adolescent patient with severe hemophilia A.

  Dragana Janic, Zeljko Smoljanic, Nada Krstovski, Lidija Dokmanovic, Predrag Rodic
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  ABSTRACT: We report on a 17-year-old patient with severe hemophilia A without inhibitors who developed abdominal bleeding after an episode of severe cough. Abdominal ultrasound showed intramural intestinal hematoma as well as large amount of peritoneal fluid appearing as blood and right hematocele. Abdominal CT revealed markedly thickened intestinal wall in sigmoidal region. Patient was managed with replacement therapy as well as peritoneal drainage with favorable outcome. This is the first report on a hematoperitoneum in a hemophiliac due to ruptured intramural sigmoidal hematoma.
  International journal of hematology 02/2009; 89(2):201-3. · 1.17 Impact Factor
• Article: Bone marrow findings in juvenile idiopathic arthritis.

  Dragana Janic, Slobodan Loncarevic, Nada Krstovski, Lidija Dokmanovic, Jelena Lazic, Predrag Rodic
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  ABSTRACT: The diagnosis of juvenile idiopathic arthritis (JIA) is an exclusion one due to heterogeneous clinical presentation and lack of specific laboratory tests. The authors investigated bone marrow of 25 untreated children with JIA at the onset of the disease. Bone marrow smears were evaluated for cell populations as well as myelodysplastic features and compared to two control groups. The characteristic of bone marrow in JIA was myeloid hyperplasia and elevated plasmocyte count. There was no difference between JIA patients and control groups in terms of myelodysplastic features. These findings can be helpful in explaining hematological alterations in JIA.
  Pediatric Hematology and Oncology 10/2008; 25(6):575-81. · 0.89 Impact Factor
• Article: T-cell acute lymphoblastic leukemia in a child with ataxia-telangiectasia: case report.

  Dragana Janic, Lidija Dokmanovic, Nada Jovanovic, Jelena Lazic
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  ABSTRACT: We present a patient with acute lymphoblastic leukemia and ataxia-telangiectasia (A-T). The 4-year-old girl is the first child of young nonconsanguineous parents of Serbian origin. Gait problems appearing in the second year of life were treated by physiotherapy. At the age of 4 she was diagnosed with T-cell acute lymphoblastic leukemia and treated according to Berlin-Frankfurt-Munster strategy. Owing to typhlitis developing after 15 days of cytotoxic treatment, frequent radiologic examinations were performed causing profound aplasia. Typhlitis did not respond to conservative treatment but necessitated extensive bowel resection. At that time the A-T was suspected by our team and confirmed by increased chromosomal radiosensitivity and markedly reduced level of A-T mutated protein. Chemotherapy was continued without alkylating agents and further radiologic imaging ran an uncomplicated course. At present, the patient is in first remission and 2.5 years since the beginning of the treatment. We stress the importance of careful initial neurologic evaluation of children with malignancy.
  Journal of Pediatric Hematology/Oncology 11/2007; 29(10):713-5. · 1.16 Impact Factor
• Article: Myeloid sarcoma presenting with bilateral proptosis and kidney infiltration.

  Dragana Janic, Nada Jovanovic, Lidija Dokmanovic, Dimitrije Brasanac, Zeljko Smoljanic, Jelena Lazic, Predrag Rodic
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  ABSTRACT: The authors describe a male infant with a history of transient pancytopenia who developed progressive bilateral proptosis associated with diffuse infiltration of the kidney and normal bone marrow. The histopathological examination of the kidney revealed diffuse infiltration of cells of myeloid origin with monocytic differentiation. Although orbital involvement by myeloid sarcoma, with or without concurrent acute myeloid leukemia, is well known, there are distinctive features in this patient that are not reported in the literature, namely bilateral proptosis and simultaneous presence of bilateral kidney infiltration, which enabled diagnosis.
  Pediatric Hematology and Oncology 04/2007; 24(2):141-8. · 0.89 Impact Factor
• Article: Analysis of thiopurine S-methyltransferase polymorphism in the population of Serbia and Montenegro and mercaptopurine therapy tolerance in childhood acute lymphoblastic leukemia.

  Lidija Dokmanovic, Jelena Urosevic, Dragana Janic, Nada Jovanovic, Branka Petrucev, Natasa Tosic, Sonja Pavlovic
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  ABSTRACT: Thiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. It is now well established that interindividual variation in sensitivity to thiopurines can be the result of the presence of genetic polymorphisms in the TPMT gene. The aim of this study was to determine the frequency and type of TPMT polymorphisms in the population of Serbia and Montenegro and to assess its relevance in the management of childhood acute lymphoblastic leukemia (ALL). Blood samples from 100 healthy adults and 100 children with ALL were analyzed for common mutations in the TPMT gene using polymerase chain reaction-based assays. The results revealed that allelic frequencies were 0.2% for TPMT*2, 3.2% for TPMT*3A, and 0.5% for TPMT*3B. A rare TPMT*3B allele was detected in 2 families. No TPMT*3C allele was found. The general pattern of TPMT-variant allele distribution as well as their frequencies in the population of Serbia and Montenegro, is similar to those determined for other Slavic and Mediterranean populations. The ability to tolerate 6-mercaptopurine (6-MP) -based maintenance therapy was used as a surrogate marker of hematologic toxicity. In the study of 50 patients with childhood ALL treated according to the BFM-like protocol, it was found that even TPMT-heterozygous patients are at greater risk of thiopurine drug-related leukopenia (mean duration of period when children missed therapy as a result of leukopenia for TPMT-heterozygous patients was 11.3 weeks vs 3.4 weeks for wild-type genotype patients, P < 0.01). In another group of 50 patients, the TPMT genotype was determined prospectively. The therapy protocol was modified considering their TPMT genotype. Administering reduced 6-MP dosages in the initial phase of maintenance allowed TPMT-heterozygous patients to later receive full protocol doses of both 6-MP and nonthiopurine therapy without omitting therapy resulting from myelotoxicity. These results justify performing TPMT genotyping before initiating thiopurine therapy in all children with ALL to minimize consequent toxicity.
  Therapeutic Drug Monitoring 01/2007; 28(6):800-6. · 2.49 Impact Factor
• Article: Retroperitoneal kaposiform hemangioendothelioma with tufted angioma-like features in an infant with Kasabach-Merritt syndrome.

  Dimitrije Brasanac, Dragana Janic, Ivan Boricic, Nada Jovanovic, Lidija Dokmanovic
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  ABSTRACT: Kasabach-Merritt syndrome denotes profound thrombocytopenia and coagulopathy in an infant with a vascular tumor. A retroperitoneal vascular tumor with an unusual combination of histopathological features is reported, and compared with vascular lesions described in the reported cases of Kasabach-Merritt syndrome in the literature. A large retroperitoneal tumor that had expanded through the sigmoid mesocolon into the sigmoid colon wall was resected from an 8-month-old infant with fully developed Kasabach-Merritt syndrome. Histological examination revealed a combination of venous (cavernous) malformation, kaposiform hemangioendothelioma and tufted angioma-like areas. Cellular tumor components (especially tufted angioma-like parts) infiltrated the wall of the sigmoid colon to the submucosal level. Immunohistochemical staining with antibodies to the Ki-67 antigen and proliferating cell nuclear antigen showed a low proliferative activity, whereas the antiapoptotic bcl-2 protein was expressed diffusely in tumor cells. This is the first reported case of a vascular tumor with tufted angioma-like elements found in the retroperitoneum, and the first reported in combination with kaposiform hemangioendothelioma and venous malformation in the same lesion. Considering the immunohistochemical results and overlapping histological features, it may be considered that tufted angioma and kaposiform hemangioendothelioma represent different growth patterns or stages in the development of a single type of hemangioma.
  Pathology International 10/2003; 53(9):627-31. · 1.62 Impact Factor
• Article: Late vitamin K deficiency bleeding in an infant with choledochal cyst.

  Nada Krstovski, Dragana Janic, Lidija Dokmanovic, Jelena Lazic, Predrag Rodic, Zoran Krstic
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  ABSTRACT: Infantile choledochal cyst (CC) usually presents as jaundice, vomiting, acholic stools, and hepatomegaly, and it can resemble biliary atresia. Although bleeding tendency is a rare clinical presentation of CC, it can be the first symptom, especially in infants less than 12 months of age. We report a case of a two-month-old infant with choledochal cyst presenting as late vitamin K deficiency bleeding (VKDB). Early recognition of diseases predisposing to VKDB and immediate investigation and treatment of warning bleeds help to prevent the worst consequences. Late VKDB is often the presenting feature of a serious underlying disease that may be recognized early. The sudden onset of bleeding tendency in infants with congenital liver or biliary tract disease may suggest not only biliary atresia but also, although extremely rare, CC. Early vitamin K administration leads to rapid normalization of hemostatic parameters, which enables major liver surgery.
  The Turkish journal of pediatrics 52(6):652-4. · 0.44 Impact Factor