Mll

Mucocele-like lesions of the breast are rare, usually presenting themselves as suspicious findings on imaging, warranting biopsies. It can be associated with several degrees of hyperplasia, including atypical ductal hyperplasia and ductal carcinoma in situ, historically being considered a high-risk lesion. It also can be an underestimated invasive carcinoma in a percutaneous biopsy. When facing a histologic diagnosis of a mucocele-lesion in a percutaneous biopsy, it is important to be aware of these lesions' significance to make the most appropriate interpretation, recommendation, and management...

PURPOSE: Genetic mutations are major factors in the diagnosis and prognosis of leukemia, and it is difficult to assess these variants using single-gene analysis. Therefore, this study aimed to develop a fast and cost-effective method for genetic screening of myeloid malignancies using a customized next-generation sequencing (NGS) panel. PATIENTS AND METHODS: A customized myeloid panel was designed and investigated in 15 acute myeloid leukemia patients. The panel included 11 genes that were most commonly mutated in myeloid malignancies...

BACKGROUND: Chromosomal rearrangements involving the Mixed lineage leukemia (MLL) gene are observed in acute leukemia (AL) patients, which have poor prognosis, especially in infants. Hence, there is still a challenge to develop other effective agents to treat AL with MLL rearrangements (MLLr). MLL has been shown to rearrange with partner genes, of which the most frequently observed are AF4 and AF9. Moreover, AL is characterized by a differentiation blockage resulting in the accumulation of immature cells...

BACKGROUND: The presence of Blood-Brain Barrier (BBB) dysfunction is defined by albumin quotient (QALB ) and characterize a group of Multiple Sclerosis (MS) patients at clinical onset. We evaluated the concentration in cerebrospinal fluid (CSF) of 87 cytokines, to better characterize the CSF inflammatory pattern in presence of BBB damage. MATERIALS AND METHOD: In an exploratory cohort, CSF cytokines were evaluated by means of Multiplex technology (Bio-Plex Pro-Human Cytokine, GF and Diabetes 27-Plex Panel, Bio-Plex Pro-Human Chemokines 40-Plex Panel, Bio-Plex Pro-Human Inflammation Assays 37-Plex Panel) in a cohort of Other Not Inflammatory Neurological Disorders (ONIND) and in cohort of patients with MS, stratified according to BBB damage into QALB + and QALB - MS patients...

Pioneer transcription factors direct cell differentiation by deploying new enhancer repertoires through their unique ability to target and initiate remodelling of closed chromatin. The initial steps of their action remain undefined, although pioneers have been shown to interact with nucleosomal target DNA and with some chromatin-remodeling complexes. We now define the sequence of events that enables the pioneer Pax7 with its unique abilities. Chromatin condensation exerted by linker histone H1 is the first constraint on Pax7 recruitment, and this establishes the initial speed of chromatin remodeling...

The decline in stem cell function during aging may affect the regenerative capacity of mammalian organisms; however, the gene regulatory mechanism underlying this decline remains unclear. Here we show that the aging of neural stem and progenitor cells (NSPCs) in the male mouse brain is characterized by a decrease in the generation efficacy of proliferative NSPCs rather than the changes in lineage specificity of NSPCs. We reveal that the downregulation of age-dependent genes in NSPCs drives cell aging by decreasing the population of actively proliferating NSPCs while increasing the expression of quiescence markers...

Mixed-phenotype acute leukemias (MPAL) account for < 4% of all cases of acute leukemias. These are a heterogeneous group of leukemias grouped together by the WHO classification as "rare subtypes." The diagnosis and treatment of MPAL is extremely challenging particularly for low middle income countries. Of these, B/myeloid and T/myeloid combinations are relatively common subtypes. However, megakaryoblastic and erythroid lineages in combination with other lineages are still rare enough to not even be addressed in the WHO classification...

BACKGROUND: Inhibition of cyclin-dependent kinase 9 (CDK9), a novel epigenetic target in cancer, can reactivate epigenetically silenced genes in cancer by dephosphorylating the SWI/SNF chromatin remodeler BRG1. Here, we characterized the anti-tumor efficacy of MC180295, a newly developed CDK9 inhibitor. METHODS: In this study, we explored the pharmacokinetics of MC180295 in mice and rats, and tested the anti-tumor efficacy of MC180295, and its enantiomers, in multiple cancer cell lines and mouse models...

The lysine(K)-specific methyltransferase 2A gene ( KMT2A ), previously known as mixed lineage leukemia ( MLL ), frequently rearranged in acute leukemia, belongs to one of the most promiscuous genes and has been found fused to more than 80 different partners. KMT2A :: SEPTIN6 fusion is a relatively uncommon rearrangement observed in pediatric acute myeloid leukemia (AML) patients, some of which may harbor other mutations. We herein report a case of AML-M4-infant with KMT2A :: SEPTIN6 fusion and DIS3 variant...

Massive localized lymphedema (MLL) is a rare disease caused by the obstruction of lymphatic vessels with specific clinical morphological and radiological characteristics. People with morbid obesity are mainly affected by MLL. Lymphedema is easily confused with soft tissue sarcoma and requires differential diagnosis, both the possibility of an MLL and also carcinoma manifestations in the soft tissues. The possible causes of massive lymphedema include trauma, surgery, and hypothyroidism. This report is the first case of MLL treated surgically in the Russian Federation...

The landscape of chromosomal aberrations in the tumor cells of the patients with B-ALL is diverse and can influence the outcome of the disease. Molecular karyotyping at the onset of the disease using chromosomal microarray (CMA) is advisable to identify additional molecular factors associated with the prognosis of the disease. Molecular karyotyping data for 36 patients with Ph-negative B-ALL who received therapy according to the ALL-2016 protocol are presented. We analyzed copy number alterations and their prognostic significance for CDKN2A / B , DMRTA , DOCK8 , TP53 , SMARCA2 , PAX5 , XPA , FOXE1 , HEMGN , USP45 , RUNX1 , NF1 , IGF2BP1 , ERG , TMPRSS2 , CRLF2 , FGFR3 , FLNB , IKZF1 , RUNX2 , ARID1B , CIP2A , PIK3CA , ATM , RB1 , BIRC3 , MYC , IKZF3 , ETV6 , ZNF384 , PTPRJ , CCL20 , PAX3 , MTCH2 , TCF3 , IKZF2 , BTG1 , BTG2 , RAG1 , RAG2 , ELK3 , SH2B3 , EP300 , MAP2K2 , EBI3 , MEF2D , MEF2C , CEBPA , and TBLXR1 genes, choosing t(4;11) and t(7;14) as reference events...

BACKGROUND: The involvement of the KMT2 methyltransferase family in the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains elusive. METHOD: This study adhered to the PRISMA guidelines, employing a search strategy in the LIVIVO, PubMed, Scopus, Embase, Web of Science, and Google Scholar databases. The methodological quality of the studies was assessed by the Joanna Briggs Institute. RESULTS: A total of 33 studies involving 4294 individuals with HNSCC were included in this review...

Lymphoid-primed multipotent progenitor (LMPP)-like and granulocyte-monocyte progenitor (GMP)-like leukemia stem cells (LSCs) co-exist in the blood of most patients with acute myeloid leukemia (AML). Complete elimination of both types of LSCs is required to cure AML. Using an MLL-AF9-induced murine AML model, we studied the role of hematopoietic cytokines in the survival of LMPP- and GMP-like LSCs. We found that SCF or FLT3L promotes the survival of LMPP-like LSCs by stimulating Stat5-mediated Mcl1 expression, whereas interleukin-3 (IL-3) or IL-6 induces the survival of GMP-like LSCs by stimulating Stat3/nuclear factor κB (NF-κB)-mediated Bcl2 expression...

A Morel-Lavallee lesion (MLL) is a rare internal denudement injury of skin and hypodermis from deep fascia, usually occurring hours to days after an inciting trauma. A common location is the pelvis or thigh where there is prominent vascularization and may mimic diagnoses such as deep vein thrombosis or contusion. Fluid collections that persist despite conservative management require surgical intervention and frequent and prolonged hospitalizations as in this case of a patient with a persistent MLL. We emphasize early imaging for diagnosis and surgical service involvement, as delay may lead to persistent symptoms and worse health outcomes...

In patients with acute myeloid leukemia (AML), about 25%-35% of patients have a history of other hematological diseases, 10% of patients have a history of malignant tumors in other systems and have received cytotoxic treatment including chemotherapy and/or radiation, and the disease is categorized as therapy-related acute myeloid leukemia (t-AML) according to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. Two subsets of t-AML are generally recognized based on the nature of prior treatments and the characteristics of the disease...

Morel-Lavallée lesions are uncommon soft tissue injuries resulting from trauma, characterized by the separation of subcutaneous tissue from the underlying fascia. Soft tissue infections with Pseudomonas aeruginosa are rare and most typically associated with hospital-acquired infections and burn wounds. This case report is regarding a 57-year-old man following a motorcycle accident who presented with a unique occurrence of an MLL complicated by P. aeruginosa infection. The patient underwent extensive treatment over the course of months, which may have been prevented with a better understanding of the injury...

The heterogeneity of acute myeloid leukemia (AML), a complex hematological malignancy, is caused by mutations in myeloid cells affecting their differentiation and proliferation. Thus, various cytogenetic alterations in AML cells may be characterized by a unique metabolome and require different treatment approaches. In this study, we performed untargeted metabolomics to assess metabolomics differences between AML patients and healthy controls, AML patients with different treatment outcomes, AML patients in different risk groups based on the 2017 European LeukemiaNet (ELN) recommendations for the diagnosis and management of AML, AML patients with and without FLT3-ITD mutation, and a comparison between patients with FLT3-ITD, CBF-AML (Core binding factor acute myelogenous leukemia), and MLL AML (mixed-lineage leukemia gene) in comparison to control subjects...

OBJECTIVE: To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML). METHODS: The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed...

The start-up and stable operation of partial nitritation-anammox (PN/A) treatment of mature landfill leachate (MLL) still face challenges. This study developed an innovative staged pilot-scale PN/A system to enhance nitrogen removal from MLL. The staged process included a PN unit, an anammox upflow enhanced internal circulation biofilm (UEICB) reactor, and a post-biofilm unit. Rapid start-up of the continuous flow PN process (full-concentration MLL) was achieved within 35 days by controlling dissolved oxygen and leveraging free ammonia and free nitrous acid to selectively suppress nitrite-oxidizing bacteria (NOB)...

Acute myeloid leukemia (AML) cell survival and chemoresistance are influenced by the existence of bone marrow mesenchymal stem cells (BMMSCs); however, the pathways by which BMMSCs contribute to these processes remain unclear. We earlier revealed that methyltransferase-like 3 (METTL3) expression is significantly reduced in AML BMMSCs and that METTL3 mediates BMMSC adipogenesis to promote chemoresistance in human AML cell lines in vitro. In this investigation, we evaluated the METTL3 function in vivo. Mice exhibiting a conditional removal of Mettl3 in BMMSCs were developed by mating Prrx1-CreERT2 ;Mettl3fl/+ mice with Mettl3fl/fl mice using the CRISPR-Cas9 system...