Lack of TP53 and FMS gene mutations in children with myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are rare disorders in children. Molecular mechanisms underlying MDS in children are not yet completely understood. Considering the role of FMS and TP53 gene mutations in adult MDS patients, we analyzed mutations of these genes in a cohort of 35 children with MDS.

Molecular basis of thalassemia syndromes in Serbia and Montenegro.

This study reports the molecular characterization of thalassemia syndromes in Serbian and Montenegrin populations. We identified eight beta-thalassemia mutations [codon 39 (C-->T), IVS-I-110 (G-->A), IVS-II-745 (C-->G), codon 44 (-C), -87 (C-->G), IVS-II-1 (G-->A), IVS-I-6 (T-->C), IVS I-1 (G-->A)] in 70 members of 29 families using polymerase chain reaction, reverse dot blot, amplification refractory mutation system and direct sequencing analysis. Hemoglobin (Hb) Lepore was found to be the most common cause of the thalassemia phenotype.

[Molecular characteristics of the thalassemia syndrome and prenatal diagnosis in a high risk family].

The diagnosis of thalassaemia maior has been established in a 6 months old infant by screenig tests. The sick child and his parents were included in the study. Reverse dote blot and allelle-specific PCR confirmed that the mother was heterozygous for mutation in the first intone of beta-globin chain at position 110-beta-IVSI-110.

[Primary myelodysplastic syndrome in children].

Primary MDS is a group of heterogenous clonal haematopoetic disorders. In a third of patients MDS terminates as acute myeloid leukaemia, usually resisitant to treatment, while the others succumb due to infections and haemorrhage. Conservative managements of MDS (chemotherapy, haematopoetic growth factors, modulation of cytokine network) are unsuccessful, while the bone marrow transplantation is the only definite treatment.

Low frequency of NRAS and KRAS2 gene mutations in childhood myelodysplastic syndromes.

In children, myelodysplastic syndromes (MDS) represent less then 10% of all hematological malignancies; consequently, molecular genetic studies dealing with this group of patients are scarce. We have analyzed 35 archival bone marrow samples of children with MDS for the presence of mutations in the first and second exons of the NRAS and KRAS2 genes. Mutations were detected with single-strand conformation polymorphism analysis in three patients.

Severe central nervous system thrombotic events in hemoglobin Sabine patient.

Hemoglobin (Hb) Sabine is a rare, unstable Hb variant resulting from the point mutation in codon 91 (CTG --> CCG) of beta-globin gene. We report a case of Hb Sabine patient with mild hemolytic anemia, unusually high Hb F level and severe central nervous system thrombotic disturbances. We have tried to elucidate possible genetic background of this unusual Hb Sabine phenotype.

[Adhesion molecules in Wilm's tumor: expression and significance of beta-catenin (part II)].

Beta-catenin is a glicoprotein which has an important role in cell-cell adhesion, as well as in cell signal transmission, in u regulation of gen expression and in interaction with axin and APC (adenomatous poliposis coli). Its oncogenic role in several types of carcinomas in human population is well known. It is very likely that beta-catenin as an protooncogen plays an important role in genesis of Wilms tumor.

[Corticoid-sensitive nephrotic syndrome in children with myelodysplastic syndromes].

Several reports have documented various forms of glomerular diseases in adults with myelodysplastic syndromes (MDS), but similar reports in children are lacking. We describe two children with MDS-associated with steroid-responsive nephrotic syndrome (NS). Patient 1, who had MDS with myelofibrosis, presented also hepatosplenomegaly, pancytopenia, chronic hepatitis, moderate proteinuria, hypocomplementamia and elevated ANA titer.

Glomerular involvement in myelodysplastic syndromes.

Several reports have documented various forms of glomerular diseases in adults with myelodysplastic syndromes (MDS), but similar reports in children are lacking. We describe two children with MDS-associated steroid-responsive nephrotic syndrome (NS). Patient 1, who had MDS with myelofibrosis, presented with hepatosplenomegaly, pancytopenia, chronic hepatitis, moderate proteinuria, hypocomplementemia and elevated ANA titer.

Haploidentical bone marrow transplantation in leukemia and genetic diseases.

From 1986 to June 2000, sixty children suffering from acute and chronic leukemia (n = 42, 33 of which in resistant relapse), genetic diseases (n = 11), aplastic anemia (n = 2, one of which with platelet refractoriness and bleeding), myelodysplasia (n = 5) received an haploidentical bone marrow, mismatched for 2-3 HLA loci. The donor's marrow was treated in vitro with vincristine and methylprednisolone to obtain a functional T depletion (MLC and CTL inhibition, functional blockade of Th1 and Th2). The prevalence of infectious complications and GVHD was similar to that recorded in matched unrelated donor (MUD) transplants.

[Congenital mesoblastic nephroma].

Four children with congenital mesoblastic nephroma were treated at the Children's University Hospital in Belgrade, between 1979 and 1990. In relation to the total number of children cured from renal tumours (44), diagnosis of congenital mesoblastic nephroma was confirmed in 9% of all cases with renal tumours. The age of all diagnosed patients was under one year.

[Major and minor congenital anomalies in children with Wilms' tumor].

Wilms's tumour is a paediatric tumour of hereditary origin in 40% of cases. In children with Wilms's tumour associated congenital anomalies are frequent, particularly congenital anomalies of the kidney and urogenital tract. Over the period from 1972 to 1987 the authors carried out a prospective study and systematically investigated congenital major and minor anomalies in 24 children with Wilms's tumour.

[Clinical manifestations of neuroblastoma in children and their effect on prognosis].

There are many prognostic factors in neuroblastoma. In this paper we analyzed the prognostic importance of some clinical factors like age, stage of disease, primary localization and neurological manifestations in children with neuroblastoma. We analyzed 58 children with neuroblastoma who were treated from 1970 to 1988 at the Haematology Department of Children's University Hospital in Belgrade.

[The May-Hegglin anomaly].

The paper presents a patient J.S., aged 2 1/2 years, with thrombocytopenia, presence of giant thrombocytes and basophile inclusions in the granulocytes.

[Disseminated intravascular coagulation (D.I.C.) and fibrinolysis in patients with acute leukemia (author's transl)].

Biological symptoms of D.I.C.

[Burkitt's lymphoma].

The paper presents two patients with malignant lymphoma of Burkitt's type. Initial localisation of the disease on the mandible, early dissemination in the central nervous system and bone marrow infiltration with appearance of characteristic Burkitt's type blast cells enabled us to bring the diagnosis. Rapid fatal evolution of the illness in spite of the applied therapy point of the diagnosis of this rare type of malignant lymphoma.

[Disseminated intravascular coagulation (D.I.C.) and fibrinolysis in patients with acute leukemia (author's transl)].

Biological symptoms of D.I.C.

[Erythropoietin in congenital anemias in children].

The results of the erytropoietin level determination in serum and urine of patients with congenital anemias are presented and compared to the results obtained in children with acute aplastic anemias. Three patients with congenital hypoplastic anemia Diamond-Blackfan, two with Fanconi's anemia, one with congenital pancythopenia with hyperplastic marrow and five patients with acute aplastic anemia were studied. The increased serum erythropoietin level was found in every patient whose blood hemoglobin was less than 12g%.