Papers by Irina Golovleva
Cell and Tissue Banking, Jan 10, 2024
CTG18.1 repeats than healthy controls from the same population. All failed corneal grafts had CTG... more CTG18.1 repeats than healthy controls from the same population. All failed corneal grafts had CTG18.1 n ≤ 27 with a median of 18 (IQR 8.0) repeats for the longest allele. There was no statistical difference in CTG18.1 repeat lengths between failed corneal grafts and the geographically matched healthy control group. In conclusion, none of the nine failed corneal grafts in our material had CTG18.1 repeat lengths ≥ 31, a cut-off known to have a biological relevance in FECD. Thus, our results suggest that the assessment of donors and inspection of the corneal tissue before the decision for procurement is sufficient, in terms of recognizing FECD in the donor.
Human Heredity, 1997
Interferon-alpha (IFN-alpha) is a protein family controlled by altogether 26 different IFN-alpha ... more Interferon-alpha (IFN-alpha) is a protein family controlled by altogether 26 different IFN-alpha genes. We have previously described an SspI polymorphism in the IFN A17 gene and an association between the SspI A2 allele and nasopharyngeal cancer. In this paper we present data on ethnic differences with respect to IFN A17 SspI allele frequencies. Thus the frequency of the SspI A1 allele was high in two different Chinese populations (51 and 48%, respectively) and much lower (11%) in Swedes. Intermediate values were found in African Blacks (32%), Indians (25%), Saamis (29%) and Finns (24%). The very pronounced differences between major ethnic groups make the IFN A17 SspI polymorphism a very informative anthropological marker system and suggest that it may be balanced and maintained by natural selection.
Journal of Dermatological Science, Jul 1, 2012
FL [3,4]. Thus, we considered that galegine may contribute to the anti-melanogenic effect that wa... more FL [3,4]. Thus, we considered that galegine may contribute to the anti-melanogenic effect that was seen. To assess this, B16F1 cells were pretreated with galegine and the color change was observed visually. As seen in Fig. and, according to both initial macroscopic observation and measurements of melanin content, 1000 mM galegine showed a significant anti-melanogenic effect.
Blood, Nov 16, 2007
The Wilms tumor 1 gene (WT1) acts as a transcriptional activator or repressor and is important fo... more The Wilms tumor 1 gene (WT1) acts as a transcriptional activator or repressor and is important for normal development. Evidence has accumulated to show that WT1 is oncogenic in acute leukemia and in some solid tumors. WT1 has 4 major isoforms and each encoded polypeptide is thought to make a contribution to normal gene function, but no data are available on their expression in hematologic malignancies. We have analyzed the expression of WT1 and its four isoforms (A, B, C, and D) in 187 diagnostic samples from patients with leukemia or lymphoma. WT1 RNA expression was detected in 9/10 (90%) chronic myeloid leukemias (CML), in 41/47 (87%) of acute myeloid leukemias (AML), in 38/56 (68%) acute lymphoblastic leukemias (ALL) and in 22/74 (30%) of malignant lymphomas. The highest expression levels were found in pre-B ALL and in AML samples. Aggressive lymphomas were more often WT1 positive and with higher levels compared to indolent cases (p < 0.01). Only 9% of AML and ALL bone marrows in complete remission (n=22) showed detectable WT1 expression and all benign lymph nodes studied (n=11) were WT1 negative. The different WT1 isoforms demonstrated highly variable expression levels with isoform A as the most common form in all tumor types. There was no difference in isoform expression between T-ALL and B-lineage ALL. However, AML-M3 demonstrated a significantly higher expression of isoform A compared to other AML subtypes (p<0.01). T-cell lymphoma had a higher level of all isoforms than other lymphoma types (p<0.01). We observed a high concordance regarding WT1 expression levels between matched samples from peripheral blood and bone marrow in T-ALL (R=0.982, P<0.01). A significant reduction in WT1 levels was demonstrated during chemotherapy in two pediatric AML patients. In conclusion, WT1 expression was coupled to malignancy in both bone marrow and lymph node samples and thus could be considered as a potential molecular marker for minimal residual disease detection in acute leukemia. All four WT1 isoforms could be detected in most WT1 positive samples, but their functional significance remains to be clarified.
Journal of hematology and blood disorders, Feb 1, 2016
Background: Congenital dyserythropoietic anemia type III (CDA III) can be caused by mutation in K... more Background: Congenital dyserythropoietic anemia type III (CDA III) can be caused by mutation in KIF23. CDA III differs from CDA I and II in the sense that secondary hemochromatosis has not been reported. However, we have observed elevated serum ferritin in a CDA III family. Since primary hemochromatosis is common in Northern Europe we decided to screen the family for HFE mutations.
Acta Oncologica, 2007
In the present study the expression of LRIG1 (leucine rich repeats and immunoglobin-like domains ... more In the present study the expression of LRIG1 (leucine rich repeats and immunoglobin-like domains 1) and its relation to EGFR (epidermal growth factor receptor) was examined in tumour samples and adjacent non-neoplastic tissues from 30 patients with colorectal cancer. The LRIG1 gene, at chromosome 3p14, encodes an intergral membrane protein, which counteracts signalling by receptor tyrosine kinases belonging to the ERBB (epidermal growth factor receptor) family. LRIG1 is expressed in all tissues and organs analysed to date, including breast, brain, skin, kidney, spleen and colon. Overexpression of EGFR is seen in 70 Á 90% of colorectal cancers, and is associated with a poor survival. Western blot analysis showed LRIG1 upregulation in 43% and downregulation in 43% of the colorectal cancers compared to adjacent non-neoplastic tissue. No correlation was evident between LRIG1, analysed by Western Blot and the expression of EGFR analysed by immunohistochemistry. FISH (fluoroscence in situ hybridisation) analysis showed increased LRIG1 copy number in one of nine tumours. Four colorectal cancer cell lines demonstrated two LRIG1 gene copies. In conclusion, there was a great heterogeneity in the expression of the LRIG1 protein in colorectal cancer, which was not related to gene dosage of the LRIG1 gene. Further studies can be of interest to evaluate whether alteration in LRIG1 expression in colorectal cancer is of biological or clinical significance.
Gene, May 1, 2004
We have recently identified and cloned the human LRIG1 gene (formerly LIG1). LRIG1 is a predicted... more We have recently identified and cloned the human LRIG1 gene (formerly LIG1). LRIG1 is a predicted integral membrane protein with a domain organization reminiscent of the Drosophila epidermal growth factor (EGF)-receptor antagonist Kekkon-1. We have searched for additional members of the human LRIG family and identified LRIG2 (). The LRIG2 gene was localized to chromosome 1p13 and had an open reading frame of 1065 amino acids. The LRIG2 protein was predicted to have the same domain organization as LRIG1 with a signal peptide, an extracellular part containing15 leucine-rich repeats and three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail. The LRIG2 amino acid sequence was 47% identical to human LRIG1 and mouse Lrig1 (also known as Lig-1). Northern blotting and RT-PCR revealed LRIG2 transcripts in all tissues analyzed. Quantitative real-time RT-PCR showed the most prominent RNA expression in skin, uterus, ovary, kidney, brain, small intestine, adrenal gland, and stomach. Immunoblotting of COS-7 cell lysates demonstrated that heterologously expressed human LRIG2 had an apparent molecular weight of 132 kDa under reducing gel-running conditions. N-glycosidase F treatment resulted in a reduction of the apparent molecular weight to 107 kDa, showing that LRIG2 was a glycoprotein carrying N-linked oligosaccharides. Cell surface biotinylation experiments and confocal fluorescence laser microscopy demonstrated expression of LRIG2 both at the cell surface and in the cytoplasm. LRIG2 was detected in tissue lysates from stomach, prostate, lung, and fetal brain by immunoblotting. In conclusion, LRIG2 was found to be a glycoprotein which was encoded by a gene on human chromosome 1p13 and its mRNA was present in all tissues analyzed.
British Journal of Haematology, Oct 1, 2001
Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CA... more Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML and refractory anemia with excess blasts in transformation.
Acta Ophthalmologica Scandinavica, Aug 1, 2007
Purpose: To determine whether tinted contact lenses can improve visual function in patients with ... more Purpose: To determine whether tinted contact lenses can improve visual function in patients with Bothnia dystrophy (BD), a genetically defined retinal dystrophy with prolonged dark adaptation. Methods: Twelve patients with BD were fitted with the same type of soft contact lenses tinted dark brown. Visual acuity (VA), contrast vision, near vision and visual fields were tested before and 1 month after contact lens fitting. The patients completed a visual function questionnaire. The physical properties of the contact lenses were tested using spectrophotometry. Results: The patients with the lowest VA described the most obvious improvement in visual function. This group of patients preferred darker contact lenses and continued wearing their contact lenses after the study ended. The patients with the best VA preferred lighter contact lenses and a few patients in this group discontinued contact lens wear upon completion of the study. Conclusions: Visual function in BD patients was improved by dark tinted contact lenses. The optimal colour for lenses varies, depending on the season and the individual. Other patient groups with retinal dystrophies associated with prolonged dark adaptation or dysfunction of the cone system, such as cone dystrophies or achromatopsia, may also benefit from this type of contact lens.
Acta Ophthalmologica, Feb 20, 2018
Purpose: Inherited retinal dystrophies (IRDs) represent a group of progressive conditions affecti... more Purpose: Inherited retinal dystrophies (IRDs) represent a group of progressive conditions affecting the retina. There is a great genetic heterogeneity causing IRDs, and to date, more than 260 genes are associated with IRDs. Stargardt disease, type 1 (STGD1) or macular degeneration with flecks, STGD1 represents a disease with early onset, central visual impairment, frequent appearance of yellowish flecks and mutations in the ATP-binding cassette subfamily A, member 4 (ABCA4) gene. A large number of intronic sequence variants in ABCA4 have been considered pathogenic although their functional effect was seldom demonstrated. In this study, we aimed to reveal how intronic variants present in patients with Stargardt from the same Swedish family affect splicing. Methods: The splicing of the ABCA4 gene was studied in human embryonic kidney cells, HEK293T, and in human retinal pigment epithelium cells, ARPE-19, using a minigene system containing variants c.4773+3A>G and c.5461-10T>C. Results: We showed that both ABCA4 variants, c.4773+3A>G and c.5461-10T>C, cause aberrant splicing of the ABCA4 minigene resulting in exon skipping. We also demonstrated that splicing of ABCA4 has different outcomes depending on transfected cell type. Conclusion: Two intronic variants c.4773+3A>G and c.5461-10T>C, both predicted to affect splicing, are indeed disease-causing mutations due to skipping of exons 33, 34, 39 and 40 of ABCA4 gene. The experimental proof that ABCA4 mutations in STGD patients affect protein function is crucial for their inclusion to future clinical trials; therefore, functional testing of all ABCA4 intronic variants associated with Stargardt disease by minigene technology is desirable.
Journal of Dermatological Science, Apr 1, 2013
The skin is a complex ecosystem, naturally hosting numerous bacterial species, fungi and arthropo... more The skin is a complex ecosystem, naturally hosting numerous bacterial species, fungi and arthropods. Sequencing of bacterial 16S rRNA genes obtained from skin samples revealed 205 bacterial detected in HFs. In the stratum corneum both bacterial and funga species were mostly seen as separate communities. The bacteria species in the stratum corneum were represented by Gram positive cocci (n = 2) and P. acnes (n = 1). In five samples an individual hair follicle contained both funga and bacterial species. The latter were represented by P. acne (n = 3), Gram-positive and unidentified cocci (n = 2). In three o these cases fungi and bacteria showed anatomically separate e ). d
Blood, Jul 1, 1999
involving the MLL gene at chromosome 11q23 are associated with leukemia and are present in up to ... more involving the MLL gene at chromosome 11q23 are associated with leukemia and are present in up to 70% of infant leukemias. Loss of heterozygosity (LOH) has been shown for anonymous polymorphic markers at 11q23 in adult leukemias. To study LOH at the MLL locus, we have identified two new polymorphic microsatellite markers: a GAA repeat (mllGAAn) in intron 6 of the MLL gene and a GA (mllGAn) repeat in the 5Ј flanking region of the gene, approximately 2 kb upstream of the translation initiation codon. The heterozygosity index of mllGAAn is 0.54, which renders it useful for analyzing LOH. We screened two groups of leukemia patients to study LOH at the mllGAAn marker. Group A (n ؍ 18) was selected on the basis of presentation before 18 months. Cytogenetic and reverse transcriptionpolymerase chain reaction analysis showed that 9 of these 18 children had translocations involving MLL. No LOH was observed. Group B (n ؍ 36) were randomly selected children who had presented with leukemia between 1993 and 1994. Cytogenetic analysis of this group showed a variety of different chromosomal abnormalities. LOH was shown in 9 of 20 individuals (45%) who were informative. Microsatellite instability (MSI) was demonstrated in 1 of 18 individuals in group A and 5 of 36 individuals (13.9%) in group B. MSI and LOH were observed simultaneously in three individuals. Loss of an allele was confirmed in one individual by fluorescence in situ hybridization. Individuals with MSI or LOH at mllGAAn were selected for analysis at anonymous polymorphic markers D11S1364 and D11S1356, which flank the MLL gene. No LOH or MSI was observed at these markers in those individuals who were informative. These results show that LOH at the MLL gene locus is a common event during leukemogenesis. Furthermore, the presence of MSI at this locus suggests that the region is a hotspot for genetic instability. 1999 by The American Society of Hematology. ACKNOWLEDGMENT We are grateful to E. Grace and M. McKinley for providing samples, and to Christine Harrison for providing cytogenetic data on those samples.
Vision Research, Nov 1, 2003
a a, S-901 85 Ume a a, Sweden
Human Mutation, Mar 31, 2015
Corneal dystrophies are a clinically and genetically heterogeneous group of inherited disorders t... more Corneal dystrophies are a clinically and genetically heterogeneous group of inherited disorders that bilaterally affect corneal transparency. They are defined according to the corneal layer affected and by their genetic cause. In this study, we identified a dominantly inherited epithelial recurrent erosion dystrophy (ERED)-like disease that is common in northern Sweden. Whole-exome sequencing resulted in the identification of a novel mutation, c.2816C>T, p.T939I, in the COL17A1 gene, which encodes collagen type XVII alpha 1. The variant segregated with disease in a genealogically expanded pedigree dating back 200 years. We also investigated a unique COL17A1 synonymous variant, c.3156C>T, identified in a previously reported unrelated dominant ERED-like family linked to a locus on chromosome 10q23-q24 encompassing COL17A1. We show that this variant introduces a cryptic donor site resulting in aberrant pre-mRNA splicing and is highly likely to be pathogenic. Bi-allelic COL17A1 mutations have previously been associated with a recessive skin disorder, junctional epidermolysis bullosa, with recurrent corneal erosions being reported in some cases. Our findings implicate presumed gain-of-function COL17A1 mutations causing dominantly inherited ERED and improve understanding of the underlying pathology.
Journal of Interferon and Cytokine Research, Oct 1, 1997
... IRINA GOLOVLEVA,1 MICHEL BIASOTTO,2·4 ELISABETH VERPY,2 GÖRAN ROOS,3 TOMMASO MEO,2-4 MARIO TO... more ... IRINA GOLOVLEVA,1 MICHEL BIASOTTO,2·4 ELISABETH VERPY,2 GÖRAN ROOS,3 TOMMASO MEO,2-4 MARIO TOSI,2 and ERIK LUNDGREN1 ABSTRACT ... Page 4. 640 GOLOVLEVA ET AL. Tarle 2. Specific PCR-FAMA Primers for IFNA Genes ...
Genes, Chromosomes and Cancer, 2004
To gain further insight into the molecular events responsible for the extended life span and immo... more To gain further insight into the molecular events responsible for the extended life span and immortalization of human lymphoid cells, we analyzed a series of spontaneously immortalized, IL2-dependent human T-cell lines using molecular cytogenetic techniques. Two of the cell lines were derived from normal spleen and three from patients with Nijmegen breakage syndrome (NBS), a recessive disorder characterized by a high incidence of lymphoid malignancies. Here we show that spontaneous immortalization of the five T-cell lines was associated with the acquisition of copy number gains involving chromosomal region 2p13-24 as common early alterations. In addition, we found an amplification of 8q21-24 after prolonged propagations in all three NBS-derived cell lines as well as early development of near-tetraploidy in two of these lines. Gains involving the short arm of chromosome 2 recently were found in several lymphoid malignancies. Therefore, the cell lines described here can be used for identification and characterization of genes involved in the pathogenesis of lymphoid neoplasms and would also provide a useful tool for better understanding the mechanisms responsible for cell immortalization.
European Journal of Haematology, Mar 26, 2003
Although the natural history of essential thrombocythaemia (ET) includes a propensity for the dev... more Although the natural history of essential thrombocythaemia (ET) includes a propensity for the development of acute leukaemia, spontaneously occurring acute leukaemia seems to be a rare event in untreated ET (1, 2). However, secondary acute leukaemia, myelodysplastic syndrome (MDS), or solid tumours have been reported in 8-13% of ET patients treated with hydroxyurea (3). The risk of transformation seems to be highest in patients treated with more than one chemotherapeutic agent . CML emerging in patients previously diagnosed with ET has not been reported previously. This report represents a case of ET with typical clinical manifestation, typical morphology, and repeatedly normal karyotype who was treated with hydroxyurea for 18 yr and then developed Philadelphia-positive CML.
Springer eBooks, Dec 28, 2009
Retinal degenerations represent a heterogeneous group of disorders affecting the function of the ... more Retinal degenerations represent a heterogeneous group of disorders affecting the function of the retina. The frequency of retinitis pigmentosa (RP) is 1/3500 worldwide, however, in northern Sweden it is 1/2000 due to limited migration and a 'founder' effect. In this study we identified genetic mechanisms underlying autosomal dominant and recessive RP present in northern Sweden. Several novel mutations unique for this region were found. In an autosomal recessive form of RP, Bothnia dystrophy caused by mutations in the RLBP1 gene, bi-allelic mutations R234W, M226K and compound heterozygosity, M226K+R234W was detected. In dominant form of RP mapped to 19q13.42 a 59 kb genomic deletion including the PRPF31 and three other genes was found. These data provide additional information on the molecular mechanisms of RP evolvement and in the future might be useful in development of therapeutic strategies. Identification of the diseasecausing mutations allowed introducing molecular genetic testing of the patients and their families into the clinical practice.
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Papers by Irina Golovleva