Mll

In the task of multiview multilabel (MVML) classification, each instance is represented by several heterogeneous features and associated with multiple semantic labels. Existing MVML methods mainly focus on leveraging the shared subspace to comprehensively explore multiview consensus information across different views, while it is still an open problem whether such shared subspace representation is effective to characterize all relevant labels when formulating a desired MVML model. In this article, we propose a novel label-driven view-specific fusion MVML method named L-VSM, which bypasses seeking for a shared subspace representation and instead directly encodes the feature representation of each individual view to contribute to the final multilabel classifier induction...

Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangements (MLL-r) is an aggressive subtype of blood cancer with dismal prognosis, underscoring the urgent need for novel therapeutic strategies. E1A-binding protein (EP300) and CREB-binding protein (CREBBP) function as essential transcriptional coactivators and acetyltransferases, governing leukemogenesis through diverse mechanisms. Targeting EP300/CREBBP holds great promise for treating leukemia with some certain cytogenetic abnormalities...

Runt domain transcription factor 3 (RUNX3) suppresses many different cancer types and is disabled by mutations, epigenetic repression, or cytoplasmic mislocalization. In this study, we investigated whether oxidative stress is associated with RUNX3 accumulation from the nucleus to the cytoplasm in terms of histone modification. Oxidative stress elevated histone deacetylase (HDAC) level and lowered that of histone acetyltransferase. In addition, oxidative stress decreased the expression of mixed lineage leukemia (MLL), a histone methyltransferase, but increased the expression of euchromatic histone-lysine N-methyltransferase 2 (EHMT2/G9a), which is also a histone methyltransferase...

The chromatin-associated protein WD Repeat Domain 5 (WDR5) is a promising target for cancer drug discovery, with most efforts blocking an arginine-binding cavity on the protein called the 'WIN' site that tethers WDR5 to chromatin. WIN site inhibitors (WINi) are active against multiple cancer cell types in vitro, the most notable of which are those derived from MLL-rearranged (MLLr) leukemias. Peptidomimetic WINi were originally proposed to inhibit MLLr cells via dysregulation of genes connected to hematopoietic stem cell expansion...

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The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML...

BACKGROUND: Lysine [K] methyltransferase 2A (KMT2A, previously known as MLL) gene rearrangements are common in acute leukemias of various lineages and are associated with features such as chemotherapy resistance and rapid relapse. KMT2A::CBL is a rare fusion of unknown pathogenesis generated by a unique interstitial deletion of chromosome 11 that has been reported across a wide age range in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. The leukemogenic effect of the KMT2A::CBL rearrangement and its association with clinical prognosis have not been well clarified...

A model construction of systemic acute leukemia is challenging. Herein, we established a systemic leukemia mouse model using highly immunodeficient NPG mice without any immunosuppressive treatments. NPG mice received tail intravenous injection of SHI-1 cells at the concentration of 1×107 cells (group A) or 5×107 cells (group B) and randomly sacrificed each seven days post-inoculation. Tumor development was monitored using nested-PCR, peripheral blood-smear analysis, flow cytometry, pathological examinations, and immunohistochemistry...

OBJECTIVE: The objective of this study was to compare the efficacy of Biosilicate and Duraphat in the treatment of dentin hypersensitivity (DH). METHODS AND MATERIALS: This clinical trial was conducted with young adults presenting DH. A visual analogue scale (VAS) was used to assess the level of pain, using volatile and tactile tests. Forty participants presenting two teeth with DH were included, and these teeth were divided into two groups according to the treatment: Biosilicate or Duraphat...

Key gene mutations are essential for colorectal cancer (CRC) development; however, how the mutated tumor cells impact the surrounding normal cells to promote tumor progression has not been well defined. Here, we report that PIK3CA mutant tumor cells transmit oncogenic signals and result in malignant transformation of intestinal epithelial cells (IECs) via paracrine exosomal arachidonic acid (AA)-induced H3K4 trimethylation. Mechanistically, PIK3CA mutations sustain SGK3-FBW7-mediated stability of the cPLA2 protein, leading to the synthetic increase in AA, which is transported through exosome and accumulated in IECs...

Inhibition of menin in acute myeloid leukemia (AML) harboring histone-lysine- N -methyltransferase 2A rearrangement (KMT2Ar) or the mutated Nucleophosmin gene (NPM1c) is considered a novel and effective treatment approach in these patients. However, rapid acquisition of resistance mutations can impair treatment success. In patients with elevated retinoic acid receptor alpha (RARA) expression levels, promising effects are demonstrated by the next-generation RAR alpha agonist tamibarotene, which restores differentiation or induces apoptosis...

PURPOSE: Morel-Lavallée lesion (MLL) is a closed soft-tissue degloving injurie resulting from shear forces. With the advent of endoscopic technology and advancements in surgical techniques, innovative solutions are now available. However, there are few data on mid-term results after treatment of MLL, especially regarding arthroscopic method. The objective of this study is to evaluate the clinical outcomes of endoscopic debridement combined with percutaneous cutaneo-fascial suture in treating MLL...

Beyond their function as structural barriers, plant cell walls are essential elements for the adaptation of plants to environmental conditions. Cell walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental cues. These wall changes are perceived by plant sensors/receptors triggering adaptative responses during development and upon stress perception. Plant cell wall damage caused by pathogen infection, wounding or other stresses leads to the release of wall molecules, like carbohydrates (glycans), that function as Damage-Associated Molecular Patterns (DAMPs)...

To make a multicellular organism, genes need to be transcribed at the right developmental stages and in the right tissues. DNA sequences termed 'enhancers' are crucial to achieve this. Despite concerted efforts, the exact mechanisms of enhancer activity remain elusive. Mixed lineage leukemia (MLL or KMT2A) rearrangements (MLLr), commonly observed in cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia, produce novel in-frame fusion proteins. Recent work has shown that the MLL-AF4 fusion protein drives aberrant enhancer activity at key oncogenes in ALL, dependent on the continued presence of MLL-AF4 complex components...

OBJECTIVE: To ascertain the frequency of the MLL::AF9 gene rearrangement and its association with survival in Pakistani patients suffering from acute myeloid leukaemia (AML). STUDY DESIGN: Analytical study. Place and Duration of the Study: Department of Haematology, National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan, from 2015 to 2020. METHODOLOGY: Patients without a history of past AML chemotherapy, aged from 10 to 75 years, were included...

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...

Liposome is a promising carrier for pulmonary drug delivery and the nano-sized liposomes have been widely investigated in the treatment of lung diseases. However, there still lack the knowledge of micron-sized liposomes for lung delivery, which have more advantages in terms of drug loading and sustained drug release capacity. The micron-sized liposomes can be classified into multilamellar liposome (MLL) and multivesicular liposome (MVL) according to their microstructure, thus, this study focused on exploring how the micron-sized liposomes with different microstructure and phospholipid composition influence their interaction with the lung...

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory reactions and tissue damage in the joints. Long-term drug use in clinical practice is often accompanied by adverse reactions. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy with few side effects, offering a potential and safe therapeutic alternative for RA through the induction of immune tolerance. This study aimed to investigate the therapeutic effects of ECP on RA using a collagen-induced arthritis (CIA) murine model, as well as to explore its immunomodulatory effects in vivo...

Objective: To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Methods: This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children's Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10...

RNA-binding proteins (RBPs) are critical regulators for RNA transcription and translation. As a key member of RBPs, ELAV-like family protein 2 (CELF2) has been shown to regulate RNA splicing and embryonic hematopoietic development and was frequently seen dysregulated in acute myeloid leukemia (AML). However, the functional role(s) of CELF2 in hematopoiesis and leukemogenesis has not been fully elucidated. In the current study, we showed that Celf2 deficiency in hematopoietic system led to enhanced HSCs self-renewal and differentiation toward myeloid cells in mice...