Sirppisolukriisit - kun selkäkipu ei olekaan noidannuoli tai kuume flunssaa

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Somatic compensation of inherited bone marrow failure

Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by insufficient blood cell production and increased risk of transformation to myeloid malignancies. While genetically diverse, IBMFS are collectively defined by a cell-intrinsic hematopoietic stem cell (HSC) fitness defect that impairs HSC self-renewal and hematopoietic differentiation. In IBMFS, HSCs frequently acquire mutations that improve cell fitness, a phenomenon known as somatic compensation. Somatic compensation can occur via distinct genetic processes such as loss of the germline mutation or somatic alterations in pathways affected by the disease-causing gene. While the clinical implications of somatic compensation in IBMFS remain to be fully discovered, understanding these mutational processes can help understand disease pathophysiology and may inform future diagnostic and therapeutic approaches. In this review, we highlight current understanding about somatic compensation in IBMFS. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )Peer reviewe

Lasten ja nuorten aikuisten akuutin lymfoblastileukemian hoito kehittyy

Teema : Hematologiset syövät. English summaryPeer reviewe

Metaphyseal dysplasia without hypotrichosis' can present with late-onset extraskeletal manifestations

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Fibrinolytic Activity and Platelet Function in Subjects with Obstructive Sleep Apnoea and a Patent Foramen Ovale: Is There an Option for Prevention of Ischaemic Stroke?

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Gemtuzumab-Ozogamicin-Related Impaired Hemoglobin-Haptoglobin Scavenging as On-Target/Off-Tumor Toxicity of Anti-CD33 AML Therapy : A Report of Two Cases

Gemtuzumab-ozogamicin (GO) is a humanized anti-CD33 antibody, which is conjugated to a cytotoxic calicheamicin. It is used to treat acute myeloid leukemia (AML) in combination with chemotherapy. We describe here two GO-treated acute myeloid leukemia (AML) cases: both patients suffered from a toxic syndrome, which manifested as impaired hemoglobin-haptoglobin scavenging and accumulation of hemolysis-related products. Our observations and earlier reports indicated that the reaction was caused by GO-targeted destruction of CD33 + CD163+ monocytes/macrophages, which are responsible for the clearance of hemoglobin-haptoglobin complexes. The rise of plasma lactate dehydrogenase was an early sign of the reaction, and both patients had high levels of free plasma hemoglobin, but plasma haptoglobin and bilirubin levels were paradoxically normal. Symptoms included septic fever and abnormalities in cardiac tests and in the case of the first patient, severe neurological symptoms which required intensive care unit admittance. Therapeutic plasma exchanges supported the patients until the recovery of normal hematopoiesis. The symptoms may be easily confounded with infectious complications-related organ damage. Regarding the increasing use of gemtuzumab-ozogamicin and other emerging CD33-targeted cell therapies, we want to highlight this mostly unknown and probably underdiagnosed toxicity.Peer reviewe

A germline exome analysis reveals harmful POT1 variants in multiple myeloma patients and families

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Screening for potential undiagnosed Gaucher disease patients : Utilisation of the Gaucher earlier diagnosis consensus point-scoring system (GED-C PSS) in conjunction with electronic health record data, tissue specimens, and small nucleotide polymorphism (SNP) genotype data available in Finnish biobanks

Background: Autosomal recessive Gaucher disease (GD) is likely underdiagnosed in many countries. Because the number of diagnosed GD patients in Finland is relatively low, and the true prevalence is currently not known, it was hypothesized that undiagnosed GD patients may exist in Finland. Our previous study demonstrated the applicability of Gaucher Earlier Diagnosis Consensus point-scoring system (GED-C PSS; Mehta et al., 2019) and Finnish biobank data and specimens in the automated point scoring of large populations. An indicative point -score range for Finnish GD patients was determined, but undiagnosed patients were not identified partly due to high number of high-score subjects in combination with a lack of suitable samples for diagnostics in the assessed biobank population. The current study extended the screening to another biobank and evaluated the feasibility of utilising the automated GED-C PSS in conjunction with small nucleotide polymorphism (SNP) chip genotype data from the FinnGen study of biobank sample donors in the identification of undiagnosed GD patients in Finland. Furthermore, the applicability of FFPE tissues and DNA restoration in the next-generation sequencing (NGS) of the GBA gene were tested. Methods: Previously diagnosed Finnish GD patients eligible to the study, and up to 45,100 sample donors in Helsinki Biobank (HBB) were point scored. The GED-C point scoring, adjusted to local data, was automated, but also partly manually verified for GD patients. The SNP chip genotype data for rare GBA variants was visually assessed. FFPE tissues of GD patients were obtained from HBB and Biobank Borealis of Northern Finland (BB). Results: Three previously diagnosed GD patients and one patient previously treated for GD-related features were included. A genetic diagnosis was confirmed for the patient treated for GD-related features. The GED-C point score of the GD patients was 12.5-22.5 in the current study. The score in eight Finnish GD patients of the previous and the current study is thus 6-22.5 points per patient. In the automated point scoring of the HBBPeer reviewe

Maahanmuuttajien perinnölliset hemoglobiinipoikkeavuudet

• Pe­rin­nöl­li­set he­mog­lo­bii­ni­poik­kea­vuu­det ovat Suo­mes­sa har­vi­nais­sai­rauk­sia, ei­kä yh­del­le lää­kä­ril­le muo­dos­tu niis­tä riit­tä­vää ko­ke­mus­ta nor­maa­lin klii­ni­sen työn puit­teis­sa. • Osal­le po­ti­lais­ta tu­lee hoi­ta­mat­to­man he­mog­lo­bii­ni­poik­kea­vuu­den seu­rauk­se­na ete­ne­viä ku­dos­vau­rioi­ta, ja nii­den komp­li­kaa­tiot ovat kal­lii­ta hoi­taa. • Al­ku­diag­nos­tiik­ka teh­dään pe­rus­ter­vey­den­huol­los­sa, ja si­tä var­ten tar­vi­taan kan­sal­li­set suo­si­tuk­set. • Po­ti­laan oi­reet ja komp­li­kaa­tio­ris­kit edel­lyt­tä­vät seu­ran­nas­sa eri­tyis­tut­ki­muk­sia ja mo­niam­ma­til­li­sen työ­ryh­män tu­kea. • Hoi­don por­ras­tuk­sen ta­voit­tee­na on saa­da ris­ki­po­ti­laat vii­veet­tä tut­ki­muk­siin ja ajan­mu­kai­seen hoi­toon. Toi­saal­ta ne po­ti­laat, jot­ka ei­vät tar­vit­se seu­ran­taa, tu­li­si tun­nis­taa mah­dol­li­sim­man ajois­sa jo pe­rus­ter­vey­den­huol­los­sa.Peer reviewe