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a G-banding showing the complex karyotype, chromosomal aberrations are pointed by the arrows; (b) Whole chromosome paints (WCP) for chromosomes 7 and 15 confirmed the unbalanced nature of the translocations observed in G-banding; (c) Application of ETV1/ CEP7 and JAZF1 break-apart combined with WCP for chromosome 7 probes narrowed the breakpoint down to 7p21 and showed the ETV1 gene deletion
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Background
Children with Down syndrome (DS) have an enhanced risk of developing acute leukemia, with the most common subtype being acute megakaryoblastic leukemia (AMKL). Myeloid leukemia in Down syndrome (ML-DS) is considered a disease with distinct clinical and biological features. There are few studies focusing on the clonal cytogenetic changes...
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Objective: The objective of this study is to assess the choice of first-line and other line options, treatment outcome, and survival effects in transplant-ineligible patients with multiple myeloma (MM) in the novel anti-myeloma agents’ era. Materials and Methods: Forty-five transplant-ineligible patients with MM were evaluated retrospectively. Pati...
Citations
... TP53BP2 (1q41) [21]. Recently, new cases of DS-AML were reported with acquired additional aberrations, including extra 1q, associated with disease progression and poor outcomes [22,23]. Extra copies of 11q translocated to short arms 19p and 7p were detected in patients #1 and #2, respectively, and patient #3 had trisomy 11. ...
... The median age of patients with ML-DS is 1-1.8 years (Gamis et al., 2003;Bhatnagar et al., 2016). Majority of patients with ML-DS (72%) also carry other cytogenetic changes in addition to trisomy 21 (Forestier et al., 2008;De Souza et al., 2017). The contribution of these changes to disease development and progression is the subject of active research. ...
... The most common structural abnormalities are del(7p)/del(7q)/−7, del(16q), trisomy 8, and tetrasomy 21. However, none of these changes offer clear insights into the molecular pathogenesis of ML-DS, and their prognostic impact is also largely unknown (Forestier et al., 2008;De Souza et al., 2017;Labuhn et al., 2019). One recent study points out that +8 can be associated with inferior event-free survival in ML-DS (Uffmann et al., 2017). ...
Myeloid leukemia associated with Down syndrome (ML-DS) has a unique molecular landscape that differs from other subtypes of acute myeloid leukemia. ML-DS is often preceded by a myeloproliferative neoplastic condition called transient abnormal myelopoiesis (TAM) that disrupts megakaryocytic and erythroid differentiation. Over the last two decades, many genetic and epigenetic changes in TAM and ML-DS have been elucidated. These include overexpression of molecules and micro-RNAs located on chromosome 21, GATA1 mutations, and a range of other somatic mutations and chromosomal alterations. In this review, we summarize molecular changes reported in TAM and ML-DS and provide a comprehensive discussion of these findings. Recent advances in the development of CRISPR/Cas9-modified induced pluripotent stem cell-based disease models are also highlighted. However, despite significant progress in this area, we still do not fully understand the pathogenesis of ML-DS, and there are no targeted therapies. Initial diagnosis of ML-DS has a favorable prognosis, but refractory and relapsed disease can be difficult to treat; therapeutic options are limited in Down syndrome children by their stronger sensitivity to the toxic effects of chemotherapy. Because of the rarity of TAM and ML-DS, large-scale multi-center studies would be helpful to advance molecular characterization of these diseases at different stages of development and progression.
... Pojava ALL-a kod DS-a predstavlja bolesti koje imaju specifične kliničke i biološke značajke. Karakterizirane su višom pojavnošću u mlađoj dobi, niskom razinom blasta u koštanoj srži, somatskim mutacijama transkripcijskog faktora GATA-1 odgovornog za rast, sazrijevanje i diferencijaciju prekurzora megakariocita i eritrocita, višim postotkom izlječenja kada se liječe kemoterapijama nižeg intenziteta [7]. Studije potvrđuju da su djeca s DS-om oboljela od ALLa u većem postotku ženskog spola te su starija od 10 godina [8]. ...
... U komunikaciji s roditeljima MS treba utjecati na jačanje samopouzdanja roditelja, poticati pozitivnu percepciju glede ishoda bolesti, kao i pronalaženje jačih strana i pozitivnih mogućnosti koje postoje unutar okruženja. Učlanjenje u udruge i redovito pohađanje grupa podrške korisne su i na samom početku liječenja [7]. Djeca s Downovim sindromom oboljela od leukemije trebaju konstantnu podršku i nadzor tijekom svih faza bolesti. ...
Down syndrome [DS] is the most common chromosomal disorder in the population manifested by intellectual disabilities of varying degrees, often accompanied by disorders in organ systems. Compared to the children without DS, these children have a greater risk of developing malignancy such as acute leukemia. Leukemia is a malignancy of blood cells and lymph nodes and the most common form of cancer in children. Its treatment in children with DS is more complex compared to children without this syndrome. The complexity of a child’s condition with Down syndrome, caused by cancer, requires a holistic approach to address the difficulties both the child and the parents are facing. Providing especially emotional parent support is essential because parents are usually overwhelmed by painful and powerful emotions. Particular attention is paid to communication in order to reduce the feeling of sadness, fear, anxiety and helplessness
... The study revealed a none association between these polymorphisms and so the risk of AML in DS youngsters. The data likewise prove that it does not relate MTHFR polymorphisms to the chance of being a DS child [10]. ...
... Zaburzenia te powodują dysregulację w działaniu organizmu ludzkiego, dodatkowo zwiększona ekspresji czynników transkrypcyjnych (np. sirtuiny 1 -SIRT 1), która skutkuje nieprawidłowymi wzorcami acetylacji histonów, potwierdza istotną rolę genu DYRK 1 A w tych procesach [1, 27,40] (tab. 1). ...
Przemijająca nieprawidłowa mielopoeza (TAM) to unikalne zaburzenie komórek hematologicznych, które występuje u 5-10% noworodków z zespołem Downa (DS). TAM jest uważana za samoograniczającą się chorobę, która ujawnia się w ciągu pierwszych kilku miesięcy po urodzeniu. Blisko 20% pacjentów z TAM umiera w okresie niemowlęcym z powodu nowotworów komórek hematopoetycznych lub niewydolności wątroby z powodu włóknienia hepatocytów. Dzieci z trisomią 21 chromosomu (DS) mają wyraźnie zwiększone ryzyko rozwoju transformacji nowotworowych komórek hematopoetycznych zarówno z linii megakariocytowej (białaczka M7 wg klasyfikacji FAB – French-American-British) – mieloidalnej (Ostra białaczka szpikowa − AML) jak i limfoidalnej (ostra białaczki limfoblastyczna typu B – ALL). Unikalne cechy białaczek związanych z DS nie tylko wskazują na kluczową rolę komórek, u których wystąpiła aberracja w postaci trisomii 21 chromosomu w ich patogenezie, ale mogą pozwolić na poznanie całkiem nowych mechanizmów indukowania białaczek na poziomie komórek embrionalnych. Oznacza to, że sama trisomia 21 zmienia funkcjonowanie komórek macierzystych płodu, włącznie z komórką macierzystą hematopoezy(HSC), powodując liczne nieprawidłowości w mielopoezie i limfopoezie. Ponadto stwierdzono, że płytkowy czynnik wzrostu (PDGF) i transformujący czynnik wzrostu (TGF-β1) wykazują silną ekspresje w megakarioblastach, co może wyjaśniać zwłóknienie wątroby u pacjentów z DS, u których stwierdzono TAM. Wykazano również, że stan wątroby może pogarszać się nawet po remisji hematologicznej.
Background
Numerous different types of variations can occur in DNA and have diverse effects and consequences. The Variation Ontology (VariO) was developed for systematic descriptions of variations and their effects at DNA, RNA and protein levels.
Results
VariO use and terms for DNA variations are described in depth. VariO provides systematic names for variation types and detailed descriptions for changes in DNA function, structure and properties. The principles of VariO are presented along with examples from published articles or databases, most often in relation to human diseases. VariO terms describe local DNA changes, chromosome number and structure variants, chromatin alterations, as well as genomic changes, whether of genetic or non-genetic origin.
Conclusions
DNA variation systematics facilitates unambiguous descriptions of variations and their effects and further reuse and integration of data from different sources by both human and computers.
Background
Children with constitutional trisomy 21, i.e. Down syndrome (DS, OMIM #190685) have a 10 to 20-fold increased risk for a hematopoietic malignancy. They may suffer from acute lymphoblastic leukemia or acute myeloid leukemia (AML). AML referred to as myeloid leukemia of Down syndrome (ML-DS) is observed especially after birth at an early gestational age and characterized by enhanced white blood cell count, failure of spontaneous remission, liver fibrosis or liver dysfunction, and is significantly associated with early death. There are only few studies yet focusing on the clonal cytogenetic changes during evolution of ML-DS.
Case presentation
In a 1.4-year-old boy with DS an immunophenotype consistent with AML-M1 according to French-American-British (FAB) classification was diagnoses. Cytogenetic and molecular cytogenetic analyses revealed, besides constitutional free trisomy 21, an unbalanced translocation as der(16)t(1;16)(q25.3;q24), plus a balanced translocation t(3;20)(q25;q13.1). A poor clinical outcome was observed here.
Conclusions
To the best of our knowledge, an ML-DS case associated with identical acquired chromosomal abnormalities was not previously reported. Our findings suggest that especially partial trisomy 1q25 to 1q44 may be indicative for a poor prognosis in ML-DS.
