Olga Haus - Academia.edu (original) (raw)

Papers by Olga Haus

BMC Nephrology, May 4, 2022

Background: Gitelman Syndrome (GS) is a hereditary tubulopathy associated with a biallelic inacti... more Background: Gitelman Syndrome (GS) is a hereditary tubulopathy associated with a biallelic inactivating mutations of the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT). The typical clinical manifestation is a hypokalemic metabolic alkalosis with significant hypomagnesemia, and low urinary calcium excretion. Hypocalciuria is widely believed to be a hallmark of GS that distinguishes it from Barter's syndrome, presenting as hypercalciuria. The pathomechanism of hypocalciuria in GS is not fully elucidated. Up to date, a clinical course of GS with normocalciuria has been reported only in men, while women have a milder course of the disease with typical hypocalciuria, which is believed as the result of sex hormone. Additionally, there is a growing evidence that calcium channels of the distal nephron could be regulated by a variety of hormones, including aldosterone (Aldo). Case presentation: We present the case of a 28-year-old Caucasian woman with asymptomatic, chronic hypokalemia, hypomagnesemia, hypochloremic alkalosis and normal urinary calcium excretion. A high renin levels with normal concentration of Aldo in serum have also been found. The values of blood pressure were low. Based on genetic studies, two heterozygous mutations in the trans position were confirmed: c.2186G>T (p.Gly729Val) and c.1247G>C (p.Cys416Ser) in the SLC12A3 gene, which ultimately confirmed the diagnosis of GS. Conclusions: We report here the first case of genetically confirmed GS manifested as normocalciuria in a Caucasian woman. Thus, our result does not confirm a role of sex hormones on the level of calciuria. Based on the results of normal Aldo concentration despite high renin level in our patient, we hypothesized that Aldo may be connecting with the level of urinary calcium excretion in patients with the GS.

PubMed, 2006

The results of clinical and laboratory observations of 119 MDS patients divided acc. to FAB, and ... more The results of clinical and laboratory observations of 119 MDS patients divided acc. to FAB, and - after excluding RAEB-t and CMML groups -- of 95 patients divided accordingly to WHO classification are presented. The diagnosis of MDS was based on medical interview, physical examination, blood biochemistry, peripheral blood (PB) and bone marrow (BM) cytomorphology and cytochemistry, trephine biopsy and cytogenetic examination. All hematologic examinations were done according to routine methods. Cytogenetic analyses were carried out on BM cells from 24-48 h cultures in standard conditions. At least 15-20 GTG-banded metaphases were analyzed in every patient. The survival time (ST) of patients differed significantly between the FAB or WHO groups, with p=0.0004 for FAB and p=0.02 for WHO. The progression to AML was more common in less favorable groups, with p=0.0001 for FAB and p=0.00016 for WHO. The distribution of IPSS prognostic index among the groups showed statistically significant difference (p=0.0004 for FAB, and p=0.0001 for WHO), whereas the distribution of karyotypic abnormalities did not. However, in univariate analysis statistically significant influence on ST showed, beside the both classification systems: cytogenetics, the presence of blasts in PB, age and IPSS index. In multivariate analysis the sole independent prognostic factors were: PB blasts and cytogenetics. The authors conclude that the WHO classification offers a good prognostic tool for MDS patients. However, the karyotype and the presence of blasts in PB should always be taken into account.

Molecular Cytogenetics, Aug 10, 2020

Background: Fanconi anemia is a rare genetic disorder caused by mutations in genes which protein ... more Background: Fanconi anemia is a rare genetic disorder caused by mutations in genes which protein products are involved in replication, cell cycle control and DNA repair. It is characterized by congenital malformations, bone marrow failure, and high risk of cancer. The diagnosis is based on morphological and hematological abnormalities such as pancytopenia, macrocytic anaemia and progressive bone marrow failure. Genetic examination, often very complex, includes chromosomal breakage testing and mutational analysis. Case presentation: We present a child with clinical diagnosis of Fanconi anemia. Although morphological abnormalities of skin and bones were present from birth, diagnosis was only suspected at the age of 8. Chromosome breakage test in patient's lymphocytes showed increased level of aberrations (gaps, chromatid breaks, chromosome breaks, radial figures and rearrangements) compared to control. Next generation sequencing revealed presence of two pathogenic variants in FANCA gene, one of which was not previously reported. Conclusions: The article provides additional supportive evidence that compound biallelic mutations of FANCA are associated with Fanconi anemia. It also illustrates the utility of combination of cytogenetic and molecular tests, together with detailed clinical evaluation in providing accurate diagnosis of Fanconi anemia. This report, to the best of our knowledge, describes the first fully diagnosed FA patient in Polish population.

Central European Journal of Immunology, 2021

Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in child... more Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children. The factors predisposing to ALL remain mostly unknown. Natural killer (NK) cells are a component of innate immunity. Their role is to eliminate cells that were infected with viruses or underwent a neoplastic transformation. The activity of NK cells is regulated by their activating and inhibitory receptors, inter alia killer-cell immunoglobulin-like receptors (KIRs). The available data about a link between the incidence of ALL and KIR genotype are highly inconclusive, and further research is needed to explain whether such a relationship truly exists. The aim of this study was to analyze KIR genotype and haplotype combinations in children treated for ALL. Material and methods: The study included 49 children diagnosed with ALL at 1.2-19.8 years of age. The control group was composed of 43 healthy subjects aged between 1.2 and 21.9 years. DNA was isolated using QIAamp DNA Mini kits. KIR genotypes were identified by a polymerase chain reaction (PCR) with sequence-specific primers (SSPs). The analysis also included KIR haplotype combinations: AA, AB and BB. Results: Patients with ALL and controls did not differ significantly in the frequencies of individual KIR genes and haplotypes. However, the overall frequency of all 6 activating KIR genes in patients with ALL was significantly higher than in the controls (24.5% vs. 4.7%, p = 0.019). Conclusions: The findings presented here imply that individual KIR genes do not play a significant role in the pathogenesis of ALL. Nevertheless, a higher number of activating KIR genes may constitute a risk factor for this malignancy.

Haematologica, Nov 4, 2011

Bone Marrow Transplantation, Oct 29, 2012

Breast Cancer Research and Treatment, Jul 1, 2005

Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to ... more Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors.

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PubMed, 1994

Localization of genes coding for cytokines and their receptors correlates frequently with breakpo... more Localization of genes coding for cytokines and their receptors correlates frequently with breakpoints of chromosome aberrations in leukemogenesis and particular clinical and hematologic symptoms. In some cases a rearrangement of these genes and its relationship with disease course were proved.

Hämatologie und Bluttransfusion, 1998

t(8;21) is a chromosomal abnormality found in a part of AML-M2 cases and exceptionally in other b... more t(8;21) is a chromosomal abnormality found in a part of AML-M2 cases and exceptionally in other blood disorders. According to literature data, CR in this form of M2 is easy to obtain and therefore BMT is not recommended in the first remission. We report here on 3 patients observed in the past 3 years, in whom blood disease was firstly diagnosed as blast crisis/acceleration of CML, because of an excessive differentiation of their leukemic cells and low FAG scores. These results prompted us to diagnose BC/ACC-CML and to administer a proper therapy. However, cytogenetic examination of BM cells of the patients did not confirm the diagnosis: t(8;21) and no Ph chromosome was found in all samples examined, which enabled us to change the diagnosis. During the course of the disease a disappea-rance of t(8;21) in remissions and reappearance in relapses was revealed. t(8;21) is very rarely seen in BC-CML of M2 type and was never described in Ph(-) CML. Our observation confirm that of Yamasaki and co. that t(8;21) M2 may show an excessive differentiation of the myeloid cell line.

Acta Haematologica, 2014

cells in this patient group was significantly higher than in nonresponders. Conclusion: To achiev... more cells in this patient group was significantly higher than in nonresponders. Conclusion: To achieve optimal treatment response in CML patients, the elimination of CD34+CD117+ may be necessary through an apoptotic pathway.

Cancer genetics and cytogenetics, Jun 1, 1993

A new human malignant urologic cell line was established in vitro from a moderately differentiate... more A new human malignant urologic cell line was established in vitro from a moderately differentiated transitional cell carcinoma of the bladder and cytogenetically characterized. Repeated chromosome analyses of the cell line using conventional RHG and GTG banding and non-radioactive in situ hybridization showed a stable karyotype with a modal number of 48 and chromosomal rearrangements, some of which have not been previously described. Numerical deviation included three trisomies (+7, +8, +9) and one nullisomy (-19, -19). Structural changes involved a balanced translocation (1;5)(q12;q12), an isochromosome 3q, a 14p+, and two markers. Fluorescence in situ hybridization (FISH), using biotin-labeled alpha satellite probes for chromosome 9 or painting for chromosomes 1 and 8, applied to interphase nuclei or metaphases showed similar results to those found by conventional cytogenetic study. This cell line may be an interesting model for fuller characterization by molecular biology studies and for testing anti-cancer drugs in vitro.

Postȩpy higieny i medycyny doświadczalnej, Dec 31, 2020

Fanconi anemia (FA) is a rare genetic disease caused by mutations in genes whose protein products... more Fanconi anemia (FA) is a rare genetic disease caused by mutations in genes whose protein products are involved in important cell processes such as replication, cell cycle control and repair of DNA damage. FA is characterized by congenital malformations, bone marrow failure and high risk of cancer. Phenotypic symptoms, present in about 75% of patients, most often include such abnormalities as short stature, microcephaly, thumb and radial side of the limb defects, abnormal skin pigmentation, gastrointestinal and genitourinary defects. Progressive bone marrow failure occurs in the first decade of life, often initially with leukopenia or thrombocytopenia. The most common cancers occurring in patients with FA are myelodysplastic syndromes and acute myeloid leukemia, as well as solid tumors of the head and neck, skin, gastrointestinal system and genitourinary system. So far, 22 genes of Fanconi anemia (FANC) have been identified, which are located on the autosomal chromosomes, except for FANCB, which is located on the X chromosome. Protein products of FANC genes are the elements of Fanconi anemia pathway, which regulates DNA damage repair systems. Genetic diagnostics of Fanconi anemia should start by testing crosslinking agents: mitomycin C (MMC) or diepoxybutane (DEB) assuring differential diagnosis of chromosome instability syndromes. In patients with Fanconi anemia, an increased number of chromosomal gaps and breaks as well as specific radial structures are observed. In order to detect a mutation underlying Fanconi anemia, molecular techniques should be used, preferentially next generation sequencing (NGS).

Leukemia & Lymphoma, 2007

Postȩpy higieny i medycyny doświadczalnej, 2006

In spite of continuous progress in the therapy of acute leukemia, relapses still occur frequently... more In spite of continuous progress in the therapy of acute leukemia, relapses still occur frequently both in children and adults. The presence of cytogenetic aberrations in leukemic cells at presentation is an important prognostic factor in acute leukemia. The translocation t(9;22) and the 11q23/MLL rearrangement are related to poor prognosis, while hyperdiploidy >50 chromosomes and the translocation t(12;21) are indicators of good prognosis in acute lymphoblastic leukemia (ALL). In acute myeloid leukemia (AML), t(8;21), t(15;17), and inv(16) indicate good prognosis, whereas 5/5q-, 7/7q-, and complex karyotype indicate poor prognosis. It seems that the prognostic value of cytogenetic changes is related to differences in cellular drug resistance in ALL and, to lesser extent, in AML. Genetic profiling based on microarray analysis confirms the correlation between cytogenetic changes in leukemic cells and drug resistance in ALL. The cytogenetic profile possibly determines cellular drug resistance and final therapy outcome. Knowledge on the karyotype-related drug resistance profile might enable the use of targeted therapy in resistant/refractory acute leukemia both in children and adults.

Hämatologie und Bluttransfusion, 2003

Karyotype of blast cells at diagnosis is one of the most important prognostic factors in childhoo... more Karyotype of blast cells at diagnosis is one of the most important prognostic factors in childhood acute lymphoblastic leukemia (ALL). In 50 children cytogenetic examination was performed at diagnosis and in 22 — after an induction therapy. The cells were cultured for 24–48 h in standard conditions. At least 2 unstimulated cultures were done in all cases. To improve cytogenetic results cultures were stimulated with concanavalin A, PHA, or both, in 17 cases. In 72 examinations good quality mitoses were obtained. Chosen cell cycle parameters, DNA ploidy and blastosis were determined from the same BM aspirates. The mean values of these parameters of efficient and inefficient (from other 9 patients) cultures were compared by one-way analysis of variance (ANOVA) and Wilcoxon test. In the group of children with inefficient cultures, WBC count, blastosis and proliferative activity of BM cells were significantly lower (p. 50. In one case a near-haploidy was found. The most frequent trisomies were +8, and +21. Among structural changes were der(2) - 4x, del 6q - 4x, llq23 aberrations - 3x, i(17q) - 2x, and add 5q, add 6q, add(9)(q34), add(13)(q32), t(7;9), t(7;15), t(11;21), t(11;22), t(19;22) - in single cases. No typical translocations were found. All control analyses showed complete cytogenetic remission, independently from prognostic factors present at diagnosis. In 20 children with the diagnosis of B-lineage ALL bcr/abl fusion was examined with RT-PCR method. Bcr/abl fusion transcript was present in one patient.

Folia Histochemica Et Cytobiologica, May 8, 2009

Objective: Statins reduce lipids concentration in blood. The latest investigations show they also... more Objective: Statins reduce lipids concentration in blood. The latest investigations show they also improved the function of vascular endothelial cells (ECs). Thrombomodulin (TM) is particularly important marker of ECs activity. We investigated the in vitro effect of lovastatin on the expression level of TM gene.Methods and results: ECs were incubated for 24 h in culture medium including lovastatin in 3 concentrations: 0.1, 1.0, 10.0 mol/l. The mRNA level of TM increased in correlation with rising concentrations of lovastatin to 600 % vs. control group. Conclusions: TM is essential antithrombotic factor in endothelial cells. Lovastatin significantly raises thrombomodulin gene expression. It is important characteristics of this medicine, which prevents cardiovascular events.

Acta Haematologica Polonica, 2015

Hereditary Cancer in Clinical Practice, Oct 12, 2021

Background: A small but important proportion of patients (4-10 %) with AML have germline mutation... more Background: A small but important proportion of patients (4-10 %) with AML have germline mutations. They can cause the development of AML at an earlier age, confer a higher risk of relapse or predispose to secondary leukemias, including therapy-related leukemias. The analysis of germline mutations in a patient and his/her family is also critical for the selection of suitable family donors if the patient is a candidate for hematopoietic stem cell transplantation (HSCT). Methods: 103 unrelated consecutive patients with de novo AML were enrolled in the study. Control group consisted of 103 persons from the general population. We performed NGS sequencing of bone marrow cells and buccal swabs DNA of six genes: CEBPA, DDX41, ETV6, TERT, GATA2, and IDH2 to detect germline pathogenic mutations. Results: In the investigated group, 49 variants were detected in six genes. 26 of them were somatic and 23 germline. Germline variants were detected in all six tested genes. Eight pathogenic germline mutations were detected in 7 AML patients, in three genes: CEBPA, ETV6, and IDH2. One patient had two pathogenic germinal mutations, one in ETV6 and one in CEBPA gene. We identified one novel pathogenic germline mutation in CEBPA gene. The difference in frequency of all pathogenic germline mutations between the tested (7.77 %) and control groups (0.97 %) was statistically significant (p = 0.046). In the tested group, the median age at AML diagnosis was 11 years lower in patients with pathogenic germline mutations than in patients without them (p = 0.028). Conclusions: We showed higher frequency of CEBPA, ETV6, and IDH2 germline mutations in AML patients than in control group, which confirms the role of these mutations in the development of AML. We also showed that the median age at the onset of AML in patients with pathogenic germline mutations is significantly lower than in patients without them.