Induction of AML Preleukemic Fusion Genes in HSPCs and DNA Damage Response in Preleukemic Fusion Gene Positive Samples.

Preleukemic fusion genes (PFGs) occurring after DNA damage in hematopoietic stem progenitor cells (HSPCs) in utero often represent the initial event in the development of childhood leukemia. While the incidence of PFGs characteristic for acute lymphoblastic leukemia (ALL) was relatively well examined by several research groups and estimated to be 1-5% in umbilical cord blood (UCB) of healthy newborns, PFGs that are relevant to acute myeloid leukemia (AML) were poorly investigated. Therefore, this study is focused on the estimation of the incidence of the most frequent AML PFGs in newborns.

Autoimmune disease, familial clustering and thyroid carcinoma coexistent with autoimmune thyroiditis in children and adolescence: A cross-sectional study from the Czech Republic.

Background: The prevalence of autoimmune thyroiditis (AIT), as the most common autoimmune disease (AD) and papillary thyroid cancer (PTC) is steadily rising in children. The aim of this study was to determine the coexistence of other AD and thyroid carcinoma (TC) in AIT.

Methods: The cross-sectional study conducted at a tertiary center comprised AIT children (< 19 years).

First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G.

Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding a plasma membrane thiamine transporter protein (THTR-1). TRMA has been reported in less than 80 cases worldwide.

Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome.

GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia.

[The prospects for children with acute lymphoblastic leukemia of being cured has increased in the Czech Republic in the 21st century to 90% - outcome of the ALL-IC BFM 2002 trial].

Background: Acute lymphoblastic leukemia (ALL) is the most frequent childhood malignancy. Treatment has been unified in the middle of 1980 in the Czech Republic. In 2002-2007 children and adolescents with acute lymphoblastic leukemia were treated in an international randomized trial ALL-IC BFM 2002 in the Czech Republic.

The Czech National Diamond-Blackfan Anemia Registry: clinical data and ribosomal protein mutations update.

Diamond-Blackfan anemia is a rare inherited bone marrow failure syndrome diagnosed in early infancy that is characterized by a (a) macrocytic anemia with no other significant cytopenia, (b) reticulocytopenia, and (c) normal bone marrow cellularity with a paucity of erythroid precursors. Physical anomalies are often present. Mutations in several ribosomal proteins have been associated with the disease.

Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis.

Background: Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studies typically did not explore the prognostic impact of peripheral blood involvement and lacked samples from very early time points of induction.

Design And Methods: In this study, we employed real-time quantitative polymerase chain reaction analysis to examine minimal residual disease in 398 pairs of blood and bone marrow follow-up samples taken from 95 children with B-cell precursor acute lymphoblastic leukemia treated with the ALL IC-BFM 2002 protocol.

Identification of mutations in the ribosomal protein L5 (RPL5) and ribosomal protein L11 (RPL11) genes in Czech patients with Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital red blood cell aplasia that is usually diagnosed during early infancy. Apart from defects in red blood cell maturation, the disorder is also associated with various physical anomalies in 40% of patients. Mutations in the ribosomal protein (RP) S19 are found in 25% of patients, while mutations in other proteins of the small ribosomal subunit--RPS17 and RPS24--have been found in a fraction of patients.

Changes of serum thymidine kinase in children with acute leukemia.

Background: Thymidine kinase (TK) is involved in nucleic acid synthesis and is therefore considered to be an important proliferation tumor marker. Our main goal was to determine the significance of elevated TK levels as a relapse marker during follow-up with child patients suffering from acute leukemia.

Patients And Methods: TK serum levels in 38 children with acute leukemia (34 lymphoblastic, 4 myeloblastic) were determined using radio-receptor analysis (RRA, Immunotech, Prague, USA).

Identification of a new in-frame deletion of six amino acids in ribosomal protein S19 in a patient with Diamond-Blackfan anemia.

Ribosomal protein S19 (RPS19) is currently the only gene associated with Diamond-Blackfan anemia (DBA), a rare congenital pure red cell aplasia characterized by normochromic macrocytic anemia, reticulocytopenia, and normocellular bone marrow with a selective deficiency of erythroid precursors. RPS19 is mutated in 25% of DBA patients, but its role in DBA pathogenesis remains elusive. We have identified a novel heterozygous microdeletion in RPS19 in a DBA patient presenting with profound anemia after birth.

[Consolidation of therapy of acute myeloid leukemia with the AML-BFM 93 protocol in children in the Czech Republic].

Background: Acute myeloid leukemia (AML) in children is rare. Although more resistant to chemotherapy than acute lymphoblastic leukemia, its responsiveness and survival rates have considerably improved during the last 15 years by virtue of intensification of chemotherapy and due to the better supportive care. Relapses still remain the main cause of treatment failure.

[Improved results in children with acute lymphoblastic leukemia treated with the ALL-BFM 90 protocol in the Czech Republic].

Background: Prognosis of children with acute lymphoblastic leukaemia (ALL)--the most common cancer in childhood, has improved remarkably over the last 40 years. The authors report the treatment outcome in children with ALL cured according to ALL-BFM 90 Study protocol in the Czech Republic during the first half of nineties.

Methods And Results: Children aged 0-18 years were included into the study in 10 centers between 1990 to 1996.

[Hypergastrinemia associated with Helicobacter pylori infection and sideropenic anemia in a 15-year-old girl].

H. pylori is a major cause of primary chronic gastritis and peptic ulcer disease in children. The authors give an account of H.

A modified two-step method for cryopreservation of mouse embryos for purposes of embryo banking.

So far, more than 17,000 embryos have been frozen in the repository of the cryobank in the Institute of Molecular Genetics. The freezing of embryos from more than 20 inbred, congenic and mutant strains has been completed. For purposes of embryo banking, a modified two-step method was used.

The role of birds as definitive hosts and intermediate hosts of heteroxenous coccidians.

Sarcocystis-like oocysts-sporocysts were found in four species of owls (Asio otus, Bubo bubo, Strix aluco, and Tyto alba) and in five species of predatory birds (Accipiter gentilis, Accipiter nisus, Buteo buteo, Circus aeruginosus, Falco tinnunculus). In addition, the muscles of 15 of 41 (36.5%) pheasants (Phasianus colchicus) and one of two jays (Garrulus glandarius) were found to harbor three types of Sarcocystis.

Muscle Sarcocystosis in pheasants and first records of the genus Sarcocystis in Phasianus colchicus Linné, 1758 in Czechoslovakia.

During examination of 41 pheasants from the vicinity of Jindrichův Hradec (South Bohemia) muscle sarcocystosis was found in 15 birds (i.e., in 36.

Indirect haemagglutination reaction with Sarcocystis dispersa antigen.

A description is given of the preparation of antigen from Sarcocystis dispersa cystozoites and the procedure of the indirect haemagglutination test (IHA). The antibodies against this antigen were detected in experimentally infected mice from day 20 p.i.

Spontaneous and experimental infection of domestic rabbits by Sarcocystis cuniculi Brumpt, 1913.

In 43 animals, representing 36% of a sample of 117 domestic rabbits, antibodies to Sarcocystis were detected using indirect immunofluorescent antibody test (IFAT). Experimental transmission of the parasite from rabbit to cat and back to rabbit proved that the organism involved was Sarcocystis cuniculi Brumpt, 1913. The antibody response in experimental transmission was revealed by IFAT: the level of antibodies was generally low and the antibodies disappeared in less than 100 days p.

Sarcocystosis in cattle and sheep at Prague abattoir.

A total of 288 animal oesophagi, including 154 from cattle and 134 from sheep of various age, were examined for the presence of sarcosporidians at Prague abattoir. The material from cattle was positive in 129 cases (84%) and all the three species of sarcosporidians hitherto described from cattle were identified: Sarcocystis cruzi, S. hirsuta and S.

Contribution to the problem of cyst-producing coccidians.

The problem of life cycles of cyst-producing coccidians, mainly those of the genus Sarcocystis, from carnivorous birds has been discussed. Oocysts of the "sarcocystic" type have been recovered from 9 species of birds of prey and owls from Czechoslovakia. The course of experimental infection in a group of birds consisting of the species Tyto alba, Asio otus, Strix aluco, Buteo buteo has been described.