| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Eldeeb, Mohamed, et al.
(författare)
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A fetal tumor suppressor axis abrogates MLL-fusion-driven acute myeloid leukemia
- 2023
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 42:2
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Tidskriftsartikel (refereegranskat)abstract
- MLL-rearrangements (MLL-r) are recurrent genetic events in acute myeloid leukemia (AML) and frequently associate with poor prognosis. In infants, MLL-r can be sufficient to drive transformation. However, despite the prenatal origin of MLL-r in these patients, congenital leukemia is very rare with transformation usually occurring postnatally. The influence of prenatal signals on leukemogenesis, such as those mediated by the fetal-specific protein LIN28B, remains controversial. Here, using a dual-transgenic mouse model that co-expresses MLL-ENL and LIN28B, we investigate the impact of LIN28B on AML. LIN28B impedes the progression of MLL-r AML through compromised leukemia-initiating cell activity and suppression of MYB signaling. Mechanistically, LIN28B directly binds to MYBBP1A mRNA, resulting in elevated protein levels of this MYB co-repressor. Functionally, overexpression of MYBBP1A phenocopies the tumor-suppressor effects of LIN28B, while its perturbation omits it. Thereby, we propose that developmentally restricted expression of LIN28B provides a layer of protection against MYB-dependent AML.
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| 6. |
- Eldeeb, Tarek M., et al.
(författare)
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Novel three-dimensional chitosan-carbon nanotube–PVA nanocomposite hydrogel for removal of Cr6+ from wastewater
- 2020
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Ingår i: Desalination and Water Treatment. - : Desalination Publications. - 1944-3994. ; 184, s. 163-177
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Tidskriftsartikel (refereegranskat)abstract
- A novel hybrid nanocomposite adsorbent was prepared by encapsulation of multi-walled carbon nano-tubes within polyvinyl alcohol/chitosan hydrogel (Cs/MWCNT/PVA) and cross-linked with glu-taraldehyde. The chemical reactions between the components affected the position and intensities of the infrared bands. This nanocomposite has excellent Cr6+ ions adsorption efficiency. The optimal conditions of the process as a function of the solution pH, contact time, ionic strength, and sorbent weight were investigated. The batch equilibrium experiments revealed that the most suitable pH for chromium adsorption was at 1.5. The maximum adsorption capacity for the hydrogel was 217.4 mg g–1 as estimated by the Langmuir model. Other isotherm models, such as Freundlich and Temkin, were used to analyze the experimental data and the models’ parameters were evaluated. The pseudo-first and second-order, Elovich, intraparticle diffusion, and film diffusion kinetic models were also inves-tigated. The obtained results enabled to estimate the possibility to use the Cs/MWCNT/PVA hydrogel in the removal of Cr6+ ions from wastewater by adsorption.
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| 7. |
- Jassinskaja, Maria, et al.
(författare)
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A complex interplay of intra- and extracellular factors regulates the outcome of fetal- and adult-derived MLL-rearranged leukemia
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Ingår i: Leukemia. - 0887-6924.
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Tidskriftsartikel (refereegranskat)abstract
- Infant and adult MLL1/KMT2A-rearranged (MLLr) leukemia represents a disease with a dismal prognosis. Here, we present a functional and proteomic characterization of in utero-initiated and adult-onset MLLr leukemia. We reveal that fetal MLL::ENL-expressing lymphomyeloid multipotent progenitors (LMPPs) are intrinsically programmed towards a lymphoid fate but give rise to myeloid leukemia in vivo, highlighting a complex interplay of intra- and extracellular factors in determining disease subtype. We characterize early proteomic events of MLL::ENL-mediated transformation in fetal and adult blood progenitors and reveal that whereas adult pre-leukemic cells are mainly characterized by retained myeloid features and downregulation of ribosomal and metabolic proteins, expression of MLL::ENL in fetal LMPPs leads to enrichment of translation-associated and histone deacetylases signaling proteins, and decreased expression of inflammation and myeloid differentiation proteins. Integrating the proteome of pre-leukemic cells with their secretome and the proteomic composition of the extracellular environment of normal progenitors highlights differential regulation of Igf2 bioavailability, as well as of VLA-4 dimer and its ligandome, upon initiation of fetal- and adult-origin leukemia, with implications for human MLLr leukemia cells’ ability to communicate with their environment through granule proteins. Our study has uncovered opportunities for targeting ontogeny-specific proteomic vulnerabilities in in utero-initiated and adult-onset MLLr leukemia.
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| 8. |
- Säwen, Petter, et al.
(författare)
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Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging
- 2018
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Ingår i: Elife. - 2050-084X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age.
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| 9. |
- Yuan, Ouyang, et al.
(författare)
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A somatic mutation in moesin drives progression into acute myeloid leukemia
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:16
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) arises when leukemia-initiating cells, defined by a primary genetic lesion, acquire subsequent molecular changes whose cumulative effects bypass tumor suppression. The changes that underlie AML pathogenesis not only provide insights into the biology of transformation but also reveal novel therapeutic opportunities. However, backtracking these events in transformed human AML samples is challenging, if at all possible. Here, we approached this question using a murine in vivo model with an MLL-ENL fusion protein as a primary molecular event. Upon clonal transformation, we identified and extensively verified a recurrent codon-changing mutation (Arg(295)Cys) in the ERM protein moesin that markedly accelerated leukemogenesis. Human cancer-associated moesin mutations at the conserved arginine-295 residue similarly enhanced MLL-ENL-driven leukemogenesis. Mechanistically, the mutation interrupted the stability of moesin and conferred a neomorphic activity to the protein, which converged on enhanced extracellular signal-regulated kinase activity. Thereby, our studies demonstrate a critical role of ERM proteins in AML, with implications also for human cancer.
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| 10. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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