A rare case of chronic myeloid leukemia with secondary chromosomal changes including partial trisomy 17q21 to 17qter and partial monosomy of 16p13.3

<p>Abstract</p> <p>Background</p> <p>The so-called Philadelphia (Ph) chromosome is present in almost all cases with chronic myeloid leukemia (CML). Around 5-10% of these patients show complex translocations involving other chromosomes in addition to and/or besides chromosomes 9 and 22. As nowadays most CML cases are treated with Imatinib, variant rearrangements have in general no specific prognostic significance, though events of therapy resistance remain to be studied.</p> <p>Results</p> <p>Here we report a Ph chromosome positive patient with hematological typical chronic phase CML. Untypically, an unbalanced complex rearrangement involving chromosomes 16 and 17 leading to a deletion of 16pter and partial trisomy of 17q21 to 17qter, was identified besides a trisomy 8 and an additional Ph chromosome in a part of malignant cells.</p> <p>Conclusion</p> <p>Here a novel and cytogenetically unique case of a Ph chromosome positive CML clinically in chronic phase is reported, having complex secondary chromosomal aberrations. Thus, CML patients with complex chromosomal changes are nonetheless treatable by Imatinib.</p

Novel complex translocation involving 5 different chromosomes in a chronic myeloid leukemia with Philadelphia chromosome: a case report

<p>Abstract</p> <p>Background</p> <p>The well-known typical fusion gene BCR/ABL can be observed in connection with a complex translocation event in only 2-10% of cases with chronic myeloid leukemia (CML). As currently most CML cases are treated with Imatinib, variant rearrangements have in general no specific prognostic significance, though the emergence of therapy resistance remains to be studied.</p> <p>Results</p> <p>Here we report an exceptional CML case with complex chromosomal aberrations not observed before, involving a 5 chromosome translocation implying chromosomal regions such as 1q42, 4p14 and 5q31 besides 9q34 and 22q11.2.</p> <p>Conclusion</p> <p>The reported rearrangement developed most probably in one initial step and had no influence on a good response during Imatinib treatment.</p

Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog

Alcohol synergistically enhances the progression of liver disease and the risk for liver cancer caused by hepatitis C virus (HCV). However, the molecular mechanism of this synergy remains unclear. Here, we provide the first evidence that Toll-like receptor 4 (TLR4) is induced by hepatocyte-specific transgenic (Tg) expression of the HCV nonstructural protein NS5A, and this induction mediates synergistic liver damage and tumor formation by alcohol-induced endotoxemia. We also identify Nanog, the stem/progenitor cell marker, as a novel downstream gene up-regulated by TLR4 activation and the presence of CD133/Nanog-positive cells in liver tumors of alcohol-fed NS5A Tg mice. Transplantation of p53-deficient hepatic progenitor cells transduced with TLR4 results in liver tumor development in mice following repetitive LPS injection, but concomitant transduction of Nanog short-hairpin RNA abrogates this outcome. Taken together, our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV-induced liver oncogenesis enhanced by alcohol

Burial of two closely related infants under a “dragon stone” from prehistoric Armenia

“Dragon stones” are prehistoric basalt stelae carved with animal imagery found in Armenia and surrounding regions. These monuments have a complex history of use and reuse across millennia, and the original date of creation is still a matter of debate. In this article, we present a unique dragon stone context excavated at the site of Lchashen, Armenia, where a three-and-a-half-meter high basalt stela with an image of a sacrificed bovid was found above a burial dating to the 16th century BC. The burial stands out among hundreds from this site as the only one in connection with a “dragon stone”, and one of very few containing the remains of newborn babies. Furthermore, our analyses of ancient DNA extracted from the well-preserved skeletal remains of two 0–2-month-old individuals showed them to be second-degree related females with identical mitochondrial sequences of the haplogroup U5a1a1 lineage, thus indicating that the infants are closely related. Additionally, we assessed that the buried individuals displayed genetic ancestry profiles similar to other Bronze Age individuals from the region

Early Embryonic Chromosome Instability Results in Stable Mosaic Pattern in Human Tissues

The discovery of copy number variations (CNV) in the human genome opened new perspectives on the study of the genetic causes of inherited disorders and the aetiology of common diseases. Here, a single-cell-level investigation of CNV in different human tissues led us to uncover the phenomenon of mitotically derived genomic mosaicism, which is stable in different cell types of one individual. The CNV mosaic ratios were different between the 10 individuals studied. However, they were stable in the T lymphocytes, immortalized B lymphoblastoid cells, and skin fibroblasts analyzed in each individual. Because these cell types have a common origin in the connective tissues, we suggest that mitotic changes in CNV regions may happen early during embryonic development and occur only once, after which the stable mosaic ratio is maintained throughout the differentiated tissues. This concept is further supported by a unique study of immortalized B lymphoblastoid cell lines obtained with 20 year difference from two subjects. We provide the first evidence of somatic mosaicism for CNV, with stable variation ratios in different cell types of one individual leading to the hypothesis of early embryonic chromosome instability resulting in stable mosaic pattern in human tissues. This concept has the potential to open new perspectives in personalized genetic diagnostics and can explain genetic phenomena like diminished penetrance in autosomal dominant diseases. We propose that further genomic studies should focus on the single-cell level, to better understand the aetiology of aging and diseases mediated by somatic mutations

Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated entity?

<p>Abstract</p> <p>Background</p> <p>Small supernumerary marker chromosomes (sSMC) are present ~2.6 × 10⁶human worldwide. sSMC are a heterogeneous group of derivative chromosomes concerning their clinical consequences as well as their chromosomal origin and shape. Besides the sSMC present in Emanuel syndrome, i.e. der(22)t(11;22)(q23;q11), only few so-called complex sSMC are reported.</p> <p>Results</p> <p>Here we report three new cases of unique complex sSMC. One was a <it>de novo </it>case with a dic(13 or 21;22) and two were maternally derived: a der(18)t(8;18) and a der(13 or 21)t(13 or 21;18). Thus, in summary, now 22 cases of unique complex sSMC are available in the literature. However, this special kind of sSMC might be under-diagnosed among sSMC-carriers.</p> <p>Conclusion</p> <p>More comprehensive characterization of sSMC and approaches like reverse fluorescence in situ hybridization (FISH) or array based comparative genomic hybridization (array-CGH) might identify them to be more frequent than only ~0.9% among all sSMC.</p

The Human Genome Puzzle – the Role of Copy Number Variation in Somatic Mosaicism

The discovery of copy number variations (CNV) in the human genome opened new perspectives in the study of the genetic causes of inherited disorders and the etiology of common diseases. Differently patterned instances of somatic mosaicism in CNV regions have been shown to be present in monozygotic twins and throughout different tissues within an individual. A single-cell-level investigation of CNV in different human cell types led us to uncover mitotically derived genomic mosaicism, which is stable in different cell types of one individual. A unique study of immortalized B-lymphoblastoid cell lines obtained with 20 year interval from the same two subjects shows that mitotic changes in CNV regions may happen early during embryonic development and seem to occur only once, as levels of mosaicism remained stable. This finding has the potential to change our concept of dynamic human genome variation. We propose that further genomic studies should focus on the single-cell level, to understand better the etiology and physiology of aging and diseases mediated by somatic variations

Unbalanced chromosome 1 abnormalities leading to partial trisomy 1q in four infants with Down syndrome and acute megakaryocytic leukemia

<p>Abstract</p> <p>Background</p> <p>Children with Down syndrome (DS) have an increased risk of childhood acute leukemia, especially acute megakaryoblastic leukemia (AMKL) also called acute myeloid leukemia (AML) type M7. Here four yet unreported infants with such malignancies are reported.</p> <p>Results</p> <p>An unbalanced translocation involving chromosome 1 was identified by GTG banding in all cases. These were characterized in more detail by molecular cytogenetic approaches. Additional molecular analysis revealed in three of the four cases mutations in exon 2 of the GATA binding protein 1 (globin transcription factor 1), located in Xp11.23.</p> <p>Conclusion</p> <p>Our results corroborate that abnormalities of chromosome 1 are common in DS-associated AMKL. Whether this chromosomal region contains gene(s) involved in hematopoietic malignant transformation remains to be determined.</p

Metsamor in Armenia: the sixth season of fieldwork in 2018

Archaeological exploration of the eastern part of the settlement in Metsamor in 2018 uncovered several rectangular structures. Most of these structures were dated to the early Iron Ages I and II. Roman-period graves were recorded in the ruins of the Iron Age settlement. An anthropological assessment of human remains from three of the burials (sex, age, cranial and postcranial measurements as well as the selected paleopathologies) is presented in the appendix

Czy interwencje behawioralne mogą zwiększyć aktywność fizyczną młodych osób z mózgowym porażeniem dziecięcym? Przegląd zakresu działań

The primary goal of adaptive physical and special education is to increase the participation of individuals with special motor needs in educational and social activities. Current behavior modification and motivation techniques are based on descriptive explanations of physical activity behaviors and exercises provided by special educators to patients and parents; however, the efficacy of such techniques is largely unknown. The main purpose of this review was to determine how effective different special education techniques and behavior change interventions are for different domains of physical activity for patients with cerebral palsy spastic motor type. A scoping review of scientific/medical databases was conducted to identify relevant studies matched the pre-defined inclusion and exclusion criteria. Four studies were selected (n=173) implementing behavioral interventions across internet-based and in-person settings. Three of these studies were randomized controlled trials with pre-post differences in physical activity observed in youth with cerebral palsy following behavioral intervention, although improvements were not statistically different from controls. This scoping review collectively demonstrates that design and implementation of behavioral change interventions lead to improvements of specific motor skills and highlights the need for ongoing research in children and adults with special motor needs.Podstawowym celem adaptacyjnej edukacji fizycznej i specjalnej jest zwiększenie udziału osób ze specjalnymi potrzebami ruchowymi w działaniach edukacyjnych i społecznych. Obecnie techniki modyfikujące zachowania i motywację opierają się na wyjaśnieniach, jakich pedagodzy specjalni udzielają pacjentom i rodzicom, opisując ćwiczenia i zachowania związane z aktywnością fizyczną, niemniej jednak skuteczność tych technik jest nieznana. Podstawowym celem pracy jest określenie skuteczności różnych technik edukacji specjalnej i interwencji w zakresie zmiany zachowań w różnych domenach aktywności fizycznej pacjentów z mózgowym porażeniem dziecięcym typu spastycznego. Przeprowadzono przegląd naukowych/medycznych baz danych w poszukiwaniu stosownych badań, które odpowiadały wcześniej zdefiniowanym kryteriom włączenia i wyłączenia. W czterech wybranych badaniach (n=173) zastosowano interwencje behawioralne przeprowadzone za pomocą Internetu oraz osobiście. Trzy z badań były randomizowanymi kontrolowanymi badaniami, w których zaobserwowano różnice w aktywności fizycznej młodzieży z mózgowym porażeniem dziecięcym przed i po przeprowadzeniu interwencji behawioralnej, niemniej jednak stopień poprawy nie różnił się statystycznie od grupy kontrolnej. Przegląd wykazał, że projektowanie i wdrażanie zmian behawioralnych prowadzi do poprawy określonych umiejętności motorycznych, a także, że istnieje zapotrzebowanie na nowe badania dotyczące dzieci i dorosłych ze specjalnymi potrzebami ruchowymi