An original observation of the randombred nude rabbit with aplasia of B-lymphoid structures (absence of the follicles in lymph nodes and spleen, no Peyer's plaques). The thymus gland and the T-dependent structures in the spleen and lymph nodes were-on the contrary-well preserved. The nude skin of this genetic rabbit mutant contained large numbers of hair follicles showing almost intrafollicular retention of hairs with their subsequent dysplasia at the subepidermal and ostiopilar level.

• MeSH
• B-lymfocyty patologie   MeSH
• králíci abnormality   MeSH
• lymfatické uzliny abnormality   MeSH
• mutace MeSH
• orgánová specificita MeSH
• Peyerovy pláty abnormality   MeSH
• slezina abnormality   MeSH
• T-lymfocyty patologie   MeSH
• zvířata MeSH
• Check Tag
• králíci abnormality   MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

The authors describe two cases of chronic lympocytic leukaemia complicated by pure red cell aplasia of autoimmune origin. The first patient achieved complete recovery of erythropoiesis after short-term immunosuppression by means of cyclophosphamide and prednisone. The second patient did not respond to the same combination of immunosuppressive drugs and remission was achieved by administration of antithymocyte globulin. In the discussion the authors deal with contemporary knowledge of the pathogenesis of autoimmune erythroblastopenia and mechanismus of action of antithymocyte globulin.

• MeSH
• antilymfocytární sérum terapeutické užití   MeSH
• chronická lymfatická leukemie komplikace   MeSH
• čistá aplazie červených krvinek etiologie   terapie   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• imunosupresivní léčba * MeSH
• lidé středního věku MeSH
• lidé MeSH
• prednison aplikace a dávkování   MeSH
• senioři MeSH
• T-lymfocyty MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antilymfocytární sérum MeSH
• cyklofosfamid MeSH
• prednison MeSH

PURPOSE: Patients with DiGeorge syndrome suffer from T-lymphopenia. T-cells are important for the maturation and regulation of B-cell function. Our aim was to characterize the B-cell compartment in DiGeorge syndrome patients. METHODS: B-cell subset phenotypization using flow cytometry. Serum BAFF (B-cell activating factor) and serum anti-alpha-galactosyl IgM measurement using ELISA. Serum IgG measurement using nephelometry. RESULTS: We observed a significantly increased number of naïve B-cells and decreased number of switched memory B-cells in DiGeorge patients. Furthermore, we observed increased BAFF levels and a trend toward hypergammaglobulinemia later in life. Surprisingly, we detected a decrease in marginal zone-like (MZ-like) B-cells and natural antibodies in DiGeorge patients. CONCLUSION: The maturation of B-cells is impaired in DiGeorge patients, with high naïve and low switched memory B-cell numbers being observed. There is a clear trend toward hypergammaglobulinemia later in life, coupled with increased serum BAFF levels. Surprisingly, the T-independent humoral response is also impaired, with low numbers of MZ-like B-cell and low levels of anti-alpha-galactosyl IgM natural antibodies being detected.

• Klíčová slova
• B-cells, BAFF, DiGeorge, Marginal zone, Naïve, Switched,
• MeSH
• DiGeorgeův syndrom imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• faktor aktivující B-buňky imunologie   MeSH
• humorální imunita imunologie   MeSH
• hypergamaglobulinemie imunologie   MeSH
• imunoglobulin G imunologie   MeSH
• imunoglobulin M imunologie   MeSH
• imunologická paměť imunologie   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• podskupiny B-lymfocytů imunologie   MeSH
• předškolní dítě MeSH
• protilátky imunologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• faktor aktivující B-buňky MeSH
• imunoglobulin G MeSH
• imunoglobulin M MeSH
• protilátky MeSH
• TNFSF13B protein, human MeSH Prohlížeč

BACKGROUND: Bone marrow (BM) samples obtained from minimal residual disease (MRD)-negative children with B-cell acute lymphoblastic leukemia (B-ALL) were used in our laboratory as negative biological controls for the development of a neuroblastoma (NBL) flow-cytometric (FC) protocol. The accidental, but systematic, identification of rare cell populations (RCP) mimicking NBL cells (CD45- /CD56+ ) in these samples indicated the need for their thorough immunophenotypic identification, in order to elucidate their possible interference in NBL-MRD assessment. PROCEDURE: RCP observed in BM samples from 14 children recovering from BM aplasia due to intensive chemotherapy for B-ALL were investigated with the following markers: CD81, CD200, CD24, GD2, CD73, CD13, CD90, CD146, CD9, CD117, CD10, CD99, and NG2. BM samples from six newly diagnosed patients with NBL and an NBL cell line were simultaneously investigated as positive controls. RESULTS: The frequency of RCP in B-ALL BM samples was < 1/1 × 104 cells (bulky lysis), and their immunophenotypic profile was indicative of CD56+ mesenchymal stromal cells (MSCs) (CD45- , CD90+ , CD146+ , CD73+ ). Also, RCP expressed CD81 and CD200, simulating NBL cells. The most useful discriminative markers for CD56+ MSCs were CD13 and CD73. An appropriate protocol consisting of two tubes with seven color combinations was further proposed: SYTO-16, GD2 (first tube) or CD73 (second tube)-PE, CD24-ECD, CD13-PC5.5, CD45-PC7, CD81-APC, and CD56-APC700. CONCLUSIONS: RCP that were immunophenotypically similar to NBL were identified as CD56+ MSCs. As these cells might pose an obstacle to accurate NBL disease assessment by FC, especially MRD, an enhanced NBL-FC protocol is proposed for prospective evaluation.

• Klíčová slova
• flow cytometry, hematology/oncology, mesenchymal stromal cells, minimal residual disease, neuroblastoma,
• MeSH
• antigen CD56 metabolismus   MeSH
• antigeny CD45 metabolismus   MeSH
• imunofenotypizace MeSH
• kostní dřeň metabolismus   patologie   MeSH
• lidé MeSH
• mezenchymální kmenové buňky metabolismus   patologie   MeSH
• následné studie MeSH
• neuroblastom diagnóza   etiologie   metabolismus   MeSH
• pre-B-buněčná leukemie komplikace   metabolismus   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• prospektivní studie MeSH
• průtoková cytometrie MeSH
• reziduální nádor etiologie   metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CD56 MeSH
• antigeny CD45 MeSH
• NCAM1 protein, human MeSH Prohlížeč
• PTPRC protein, human MeSH Prohlížeč

Immune monitoring of cell therapies is a complex and evolving topic, particularly in the rapid expanding field of chimeric antigen receptor T (CAR-T) cell applications. Defining essential, recommended, and optional immune monitoring data post-CAR-T cell infusion is crucial to improve patient outcomes and inform post-treatment decisions. To address this gap, we conducted a survey-based study across centers affiliated with the European Society for Blood and Marrow Transplantation (EBMT), focusing on patients treated with European Medicines Agency (EMA)-approved CAR-T products. Building on a thorough review of the literature, we mapped the current landscape of immune monitoring practices and assessed their impact on clinical management. By defining the state of the art in the field, this work marks an initial step towards a structured harmonization process potentially able to enhance the management and outcomes of patients undergoing these immune cell therapies.

• Klíčová slova
• B cell aplasia, CAR-T cell expansion, CAR-T cells, CRS, ICANS, Immune monitoring, Immune reconstitution, Lentiviral integration, Transduction,
• MeSH
• chimerické antigenní receptory * imunologie   MeSH
• imunoterapie adoptivní * metody   škodlivé účinky   MeSH
• lidé MeSH
• monitorování imunologické metody   MeSH
• průzkumy a dotazníky MeSH
• T-lymfocyty imunologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• chimerické antigenní receptory * MeSH

Diamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia, underlied by haploinsufficient mutations in genes coding for ribosomal proteins (RP) in approximately 70% of cases. DBA is frequently associated with somatic malformations, endocrine dysfunction and with an increased predisposition to cancer. Here we present clinical and genetic characteristics of 62 patients from 52 families enrolled in the Czech and Slovak DBA Registry. Whole exome sequencing (WES) and array comparative genomic hybridization (aCGH) were employed to identify causative mutations in newly diagnosed patients and in cases with previously unrecognized molecular pathology. RP mutation detection rate was 81% (50/62 patients). This included 8 novel point mutations and 4 large deletions encompassing some of the RP genes. Malignant or predisposing condition developed in 8/62 patients (13%): myelodysplastic syndrome in 3 patients; breast cancer in 2 patients; colorectal cancer plus ocular tumor, diffuse large B-cell lymphoma and multiple myeloma each in one case. These patients exclusively harbored RPL5, RPL11 or RPS19 mutations. Array CGH is beneficial for detection of novel mutations in DBA due to its capacity to detect larger chromosomal aberrations. Despite the importance of genotype-phenotype correlation in DBA, phenotypic differences among family members harboring an identical mutation were observed.

• Klíčová slova
• Cancer, Diamond-Blackfan anemia (DBA), Mutations, Registry, Ribosomal proteins (RP),
• MeSH
• Diamondova-Blackfanova anemie komplikace   epidemiologie   genetika   MeSH
• genetické asociační studie MeSH
• lidé MeSH
• mutace * MeSH
• nádory etiologie   MeSH
• registrace MeSH
• ribozomální proteiny genetika   MeSH
• rodina MeSH
• sekvenování exomu MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH
• Názvy látek
• ribosomal protein L11 MeSH Prohlížeč
• ribosomal protein L5, human MeSH Prohlížeč
• ribosomal protein S19 MeSH Prohlížeč
• ribozomální proteiny MeSH

Diamond-Blackfan anaemia is a rare disease caused by insufficient expression of ribosomal proteins and is characterized by erythroid hypoplasia often accompanied by growth retardation, congenital craniofacial and limb abnormalities. In addition, Diamond-Blackfan anaemia patients also exhibit a number of behavioural abnormalities. In this study we describe the behavioural effects observed in a new mouse mutant carrying a targeted single amino acid deletion in the ribosomal protein RPS19. This mutant, created by the deletion of arginine 67 in RPS19, exhibits craniofacial, skeletal, and brain abnormalities, accompanied by various neurobehavioural malfunctions. A battery of behavioural tests revealed a moderate cognitive impairment and neuromuscular dysfunction resulting in profound gait abnormalities. This novel Rps19 mutant shows behavioural phenotypes resembling that of the human Diamond-Blackfan anaemia syndrome, thus creating the possibility to use this mutant as a unique murine model for studying the molecular basis of ribosomal protein deficiencies.

• MeSH
• chůze (způsob) fyziologie   MeSH
• Diamondova-Blackfanova anemie genetika   patologie   patofyziologie   MeSH
• hydrocefalus patologie   MeSH
• metoda rotující tyčky MeSH
• modely nemocí na zvířatech MeSH
• mutace genetika   MeSH
• mutantní kmeny myší MeSH
• myši inbrední C57BL MeSH
• nervosvalové spojení patologie   patofyziologie   MeSH
• nervový systém patologie   patofyziologie   MeSH
• paměť MeSH
• podmiňování (psychologie) MeSH
• pohyb MeSH
• ribozomální proteiny genetika   MeSH
• strach MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ribosomal protein S19 MeSH Prohlížeč
• ribozomální proteiny MeSH

The optimal timing of allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in first remission was offered also to patients with an FLT3-ITD (FMS-like tyrosine kinase 3-internal tandem duplication) allelic ratio >0.8, poor day +15 marrow blast clearance and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy. In the intent-to-treat (ITT) analysis, superiority of the experimental transplant strategy could not be shown with respect to overall survival (OS) or event-free survival. As-treated analyses suggest a profound effect of allogeneic HCT on OS (HR 0.73; P=0.002) and event-free survival (HR 0.67; P<0.001). In high-risk patients, OS was significantly improved after allogeneic HCT in aplasia (HR 0.64; P=0.046) and after HCT in remission (HR 0.74; P=0.03). Although superiority of one study arm could not be demonstrated in the ITT analysis, secondary analyses suggest that early allogeneic HCT is a promising strategy for patients with high-risk AML.

• MeSH
• akutní myeloidní leukemie genetika   terapie   MeSH
• alely MeSH
• dospělí MeSH
• homologní transplantace MeSH
• indukce remise MeSH
• Kaplanův-Meierův odhad MeSH
• karyotypizace MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• přežití bez známek nemoci MeSH
• recidiva MeSH
• regulace genové exprese u leukemie MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• tyrosinkinasa 3 podobná fms genetika   metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• FLT3 protein, human MeSH Prohlížeč
• tyrosinkinasa 3 podobná fms MeSH

T-cell malignancies can be divided into precursor (T-acute lymphoblastic leukemia/lymphoblastic lymphoma, T-ALL/LBL) and mature T-cell neoplasms, which are comprised of 28 different entities. Most of these malignancies are aggressive with rather poor prognosis. Prognosis of relapsed/refractory (R/R) disease is especially dismal, with an expected survival only several months after progression. Targeted therapies, such as antiCD30 immunotoxin brentuximab vedotin, antiCD38 antibody daratumumab, and anti-CCR4 antibody mogamulizumab are effective only in subsets of patients with T-cell neoplasms. T-cells equipped with chimeric antigen receptor (CAR-Ts) are routinely used for treatment of R/R B-cell malignancies, however, there are specific obstacles for their use in T-cell leukemias and lymphomas which are fratricide killing, risk of transfection of malignant cells, and T-cell aplasia. The solution for these problems relies on target antigen selection, CRISPR/Cas9 or TALEN gene editing, posttranslational regulation of CAR-T surface antigen expression, and safety switches. Structural chromosomal changes and global changes in gene expression were observed with gene-edited products. We identified 49 studies of CAR-based therapies registered on www.clinicaltrials.gov. Most of them target CD30 or CD7 antigen. Results are available only for a minority of these studies. In general, clinical responses are above 50% but reported follow-up is very short. Specific toxicities of CAR-based therapies, namely cytokine release syndrome (CRS), seem to be connected with the antigen of interest and source of cells for manufacturing. CRS is more frequent in antiCD7 CAR-T cells than in antiCD30 cells, but it is mild in most patients. More severe CRS was observed after gene-edited allogeneic CAR-T cells. Immune effector cell associated neurotoxicity (ICANS) was mild and infrequent. Graft-versus-host disease (GvHD) after allogeneic CAR-T cells from previous hematopoietic stem cell donor was also observed. Most frequent toxicities, similarly to antiCD19 CAR-T cells, are cytopenias. CAR-based cellular therapy seems feasible and effective for T-cell malignancies, however, the optimal design of CAR-based products is still unknown and long-term follow-up is needed for evaluation of their true potential.

• Klíčová slova
• CAR-T cells, T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma, T-cell lymphoma, chimeric antigen receptor (CAR), immunotherapy, therapy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In wild-type (WT) mice, epithelial apoptosis is involved in reducing the embryonic tooth number and the mesial delimitation of the first molar. We investigated whether apoptosis could also be involved in the reduction of tooth number and the determination of anomalous tooth boundaries in tabby (Ta)/EDA mice. Using serial histological sections and computer-aided 3D reconstructions, we investigated epithelial apoptosis in the lower cheek dentition at embryonic days 14.5-17.5. In comparison with WT mice, apoptosis was increased mainly mesially in Ta dental epithelium from day 15.5. This apoptosis showed a similar mesio-distal extent in all 5 morphotypes (Ia,b,c and IIa,b) of Ta dentition and eliminated the first cheek tooth in morphotypes IIa,b. Apoptosis did not appear to play any causal role in positioning inter-dental gaps. Analysis of the present data suggests that the increased apoptosis in Ta mice is a consequence of impaired tooth development caused by a defect in segmentation of dental epithelium.

• MeSH
• apoptóza fyziologie   MeSH
• ektodermální dysplazie embryologie   genetika   MeSH
• ektodysplasiny MeSH
• epitel embryologie   MeSH
• gestační stáří MeSH
• inbrední kmeny myší MeSH
• mandibula embryologie   MeSH
• membránové proteiny genetika   MeSH
• morfogeneze fyziologie   MeSH
• mutantní kmeny myší MeSH
• myši MeSH
• odontogeneze fyziologie   MeSH
• orgán skloviny embryologie   MeSH
• počítačové zpracování obrazu metody   MeSH
• tvář embryologie   MeSH
• zobrazování trojrozměrné metody   MeSH
• zubní zárodek embryologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• Eda protein, mouse MeSH Prohlížeč
• ektodysplasiny MeSH
• membránové proteiny MeSH