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https://www.readbyqxmd.com/read/28742611/a-rare-presentation-of-a-morel-lavallee-lesion-of-the-lower-leg-successfully-treated-with-ultrasound-guided-aspiration
#1
Audrey Falconi, Holly Crellin, Chelsea Tagawa
A Morel-Lavallee lesion (MLL) is a relatively rare condition that is caused by a traumatic shearing force. This force leads to a closed degloving injury of the subcutaneous tissue and fascia that creates a potential space that can fill with lymph, blood, and necrotic fat. The MLLs are traditionally seen after high impact trauma and typically located at the greater trochanter and pelvis, although recent reports have found them to be located at the knee, thigh, and lower leg. The MLLs typically present as swelling at the site of injury, which can be difficult to differentiate from several other diagnoses...
July 21, 2017: Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine
https://www.readbyqxmd.com/read/28741798/novel-orally-bioavailable-ezh1-2-dual-inhibitors-with-greater-antitumor-efficacy-than-an-ezh2-selective-inhibitor
#2
REVIEW
Daisuke Honma, Osamu Kanno, Jun Watanabe, Junzo Kinoshita, Makoto Hirasawa, Emi Nosaka, Machiko Shiroishi, Takeshi Takizawa, Isao Yasumatsu, Takao Horiuchi, Akira Nakao, Keisuke Suzuki, Tomonori Yamasaki, Katsuyoshi Nakajima, Miho Hayakawa, Takanori Yamazaki, Ajay Singh Yadav, Nobuaki Adachi
Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 function as catalytic subunits of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis...
July 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28733386/mir-99-regulates-normal-and-malignant-hematopoietic-stem-cell-self-renewal
#3
Mona Khalaj, Carolien M Woolthuis, Wenhuo Hu, Benjamin H Durham, S Haihua Chu, Sarah Qamar, Scott A Armstrong, Christopher Y Park
The microRNA-99 (miR-99) family comprises a group of broadly conserved microRNAs that are highly expressed in hematopoietic stem cells (HSCs) and acute myeloid leukemia stem cells (LSCs) compared with their differentiated progeny. Herein, we show that miR-99 regulates self-renewal in both HSCs and LSCs. miR-99 maintains HSC long-term reconstitution activity by inhibiting differentiation and cell cycle entry. Moreover, miR-99 inhibition induced LSC differentiation and depletion in an MLL-AF9-driven mouse model of AML, leading to reduction in leukemia-initiating activity and improved survival in secondary transplants...
July 21, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28723619/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#4
Tingxiong Fu, Xiuwei Lv, Qingzhi Kong, Changjing Yuan
SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28709134/bcr-abl1-like-acute-lymphoblastic-leukaemia-from-bench-to-bedside
#5
REVIEW
Judith M Boer, Monique L den Boer
Acute lymphoblastic leukaemia (ALL) occurs in approximately 1:1500 children and is less frequently found in adults. The most common immunophenotype of ALL is the B cell lineage and within B cell precursor ALL, specific genetic aberrations define subtypes with distinct biological and clinical characteristics. With more advanced genetic analysis methods such as whole genome and transcriptome sequencing, novel genetic subtypes have recently been discovered. One novel class of genetic aberrations comprises tyrosine kinase-activating lesions, including translocations and rearrangements of tyrosine kinase and cytokine receptor genes...
July 11, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28705330/mucocoele-like-lesions-is-surgical-excision-still-necessary
#6
I Dash, B Dessauvagie, M Hardie, C Saunders, E Wylie
AIM: To assess the rate of upgrade in our screening population to determine whether open excision biopsy of mucocoele-like lesions (MLL) is still required. MATERIALS AND METHODS: A retrospective review of the breast screening database from 1999-2014 was performed. RESULTS: MLL were identified on core biopsy in 113 women (0.6% of those recalled for a core biopsy). The majority (n=100, 88%) had a localised cluster of calcification prompting screening recall...
July 10, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28701730/the-mll-recombinome-of-acute-leukemias-in-2017
#7
C Meyer, T Burmeister, D Gröger, G Tsaur, L Fechina, S Renneville, R Sutton, N C Venn, M Emerenciano, M S Pombo-de-Oliveira, C Barbieri Blunck, B Almeida Lopes, J Zuna, J Trka, P Ballerini, H Lapillonne, M De Braekeleer, G Cazzaniga, L Corral Abascal, V H J van der Velden, E Delabesse, T S Park, S H Oh, M L M Silva, T Lund-Aho, V Juvonen, A S Moore, O Heidenreich, J Vormoor, E Zerkalenkova, Y Olshanskaya, C Bueno, P Menendez, S Teigler-Schlegel, U Zur Stadt, J Lentes, G Göhring, S Kustanovich, O Aleinikova, B W Schäfer, S Kubetzko, H O Madsen, B Gruhn, X Duarte, P Gameiro, E Lippert, S Bidet, J M Cayuela, E Clappier, C N Alonso, C M Zwaan, M M van den Heuvel-Eibrink, S Izraeli, L Trakhtenbrot, P Archer, J Hancock, A Möricke, J Alten, M Schrappe, M Stanulla, S Strehl, A Attarbaschi, M Dworzak, O A Haas, R Panzer-Grümayer, L Sedék, T Szczepański, S Caye, L Suarez, H Cavé, R Marschalek
Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here, we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements habe been identified so far, of which 94 TPGs are now characterized at the molecular level. Thirty-five out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene...
July 13, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28698205/an-fc-engineered-cd19-antibody-eradicates-mrd-in-patient-derived-mll-rearranged-acute-lymphoblastic-leukemia-xenografts
#8
Denis M Schewe, Ameera Alsadeq, Cornelia Sattler, Lennart Lenk, Fotini Vogiatzi, Gunnar Cario, Simon Vieth, Thomas Valerius, Sophia Rosskopf, Fabian Meyersieck, Julia Alten, Martin Schrappe, Martin Gramatzki, Matthias Peipp, Christian Kellner
Antibody therapy constitutes a major advance in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To evaluate the efficacy and the mechanisms of action of CD19 monoclonal antibody therapy in pediatric BCP-ALL, an Fc engineered CD19 antibody carrying the S239D/I332E mutation for improved effector cell recruitment (CD19-DE) was tested. Patient derived xenografts (PDX) of pediatric MLL-rearranged ALL were established in NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice. Antibody CD19-DE was efficient in prolonging the survival of NSG mice in a minimal residual disease (MRD) model...
July 11, 2017: Blood
https://www.readbyqxmd.com/read/28696855/don-t-forget-the-abdominal-wall-imaging-spectrum-of-abdominal-wall-injuries-after-nonpenetrating-trauma
#9
Shanna A Matalon, Reza Askari, Jonathan D Gates, Ketan Patel, Aaron D Sodickson, Bharti Khurana
Abdominal wall injuries occur in nearly one of 10 patients coming to the emergency department after nonpenetrating trauma. Injuries range from minor, such as abdominal wall contusion, to severe, such as abdominal wall rupture with evisceration of abdominal contents. Examples of specific injuries that can be detected at cross-sectional imaging include abdominal muscle strain, tear, or hematoma, including rectus sheath hematoma (RSH); traumatic abdominal wall hernia (TAWH); and Morel-Lavallée lesion (MLL) (closed degloving injury)...
July 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28694182/allogeneic-hematopoietic-stem-cell-transplantation-with-myeloablative-conditioning-is-associated-with-favorable-outcomes-in-mixed-phenotype-acute-leukemia
#10
Bartlomiej M Getta, Mikhail Roshal, Junting Zheng, Jae H Park, Eytan M Stein, Ross Levine, Esperanza B Papadopoulos, Ann A Jakubowski, Nancy A Kernan, Peter Steinherz, Richard J O'Reilly, Miguel-Angel Perales, Sergio A Giralt, Martin S Tallman, Brian C Shaffer
Mixed phenotype acute leukemia (MPAL) represents a poorly characterized group of acute leukemias that lack an accepted therapeutic approach and are typically associated with poor outcomes. We present our experience of genomic profiling, pre-transplant therapy and transplant outcomes for 36 well characterized pediatric and adult patients with MPAL defined according to the 2016 WHO leukemia update. A predominance of ALL-associated mutations and cytogenetic abnormalities was noted. Remission rates after induction appeared comparable among adults (20/23) and children (11/13) and among those who received ALL (10/11) or AML-type (21/25) induction...
July 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28690313/the-hdac-inhibitor-panobinostat-lbh589-exerts-in-vivo-anti-leukaemic-activity-against-mll-rearranged-acute-lymphoblastic-leukaemia-and-involves-the-rnf20-rnf40-wac-h2b-ubiquitination-axis
#11
P G Castro, E H J van Roon, S S M Pinhanços, L Trentin, P Schneider, M Kerstjens, G Te Kronnie, O Heidenreich, R Pieters, R W Stam
MLL-rearranged acute lymphoblastic leukaemia (ALL) represents an aggressive malignancy in infants (<1 year of age), associated with poor outcome. Current treatment intensification is not further possible, and novel therapy strategies are needed. Notably, MLL-rearranged ALL is characterised by a strongly deregulated epigenome and shows sensitivity to epigenetic perturbators. Here, we demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) using xenograft mouse models of MLL-rearranged ALL...
July 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28685945/evolutionary-changes-of-hox-genes-and-relevant-regulatory-factors-provide-novel-insights-into-mammalian-morphological-modifications
#12
Kui Li, Xiaohui Sun, Meixiu Chen, Yingying Sun, Ran Tian, Zhengfei Wang, Shixia Xu, Guang Yang
The diversity of body plan of mammals accelerates the innovation of lifestyles and the extensive adaptation to different habitats, including terrestrial, aerial, and aquatic habitats. However, the genetic basis of those phenotypic modifications, which occurred during mammalian evolution, remains poorly explored. In the present study, we synthetically surveyed the evolutionary pattern of Hox clusters that played a powerful role in the morphogenesis along the head-tail axis of animal embryos and main regulatory factors (Mll, Bmi1, and E2f6) that control the expression of Hox genes...
July 7, 2017: Integrative Zoology
https://www.readbyqxmd.com/read/28675638/azacitidine-successfully-maintained-the-second-remission-in-an-infant-with-kmt2a-rearranged-acute-lymphoblastic-leukemia-who-relapsed-after-unrelated-cord-blood-transplantation
#13
Ikue Chijimatsu, Yusuke Imanaka, Daisuke Tomizawa, Mariko Eguchi, Shiho Nishimura, Shuhei Karakawa, Mizuka Miki, Kazuko Hamamoto, Naoto Fujita
The outcome for infants with KMT2A (MLL)-rearranged acute lymphoblastic leukemia (MLL-r ALL) is dismal despite intensive therapy, including hematopoietic stem cell transplantation (HSCT). Epigenetic dysregulation is considered a key driver of MLL-r leukemogenesis, which theoretically supports the use of epigenetic modifiers as a treatment option. We report an infant MLL-r ALL case with post-HSCT relapse. After achieving a second remission, which was maintained for 10 months using only the DNA methyltransferase inhibitor, azacitidine, the patient successfully received the second HSCT...
July 4, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28669059/reemergence-of-translocation-t-11-19-q23-p13-1-in-the-absence-of-clinically-overt-leukemia
#14
Suguru Uemura, Akihiro Tamura, Atsuro Saito, Daiichiro Hasegawa, Nanako Nino, Takehito Yokoi, Teppei Tahara, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Keiichiro Kawasaki, Takeshi Mori, Noriyuki Nishimura, Minenori Ishimae, Mariko Eguchi, Yoshiyuki Kosaka
We report the case of a 10-year-old female with acute myeloid leukemia (AML) FAB M0 carrying a novel t(11;19)(q23;p13.1) MLL-ELL variant, in which intron 8 of MLL is fused to exon 6 of ELL. Complete remission, judged by morphology and cytogenetic analysis, was achieved after the conventional chemotherapy. Eight months after completion of therapy, the level of WT-1 in peripheral blood and the number of cells with the MLL-ELL fusion transcript resurged. However, the patient remained overtly healthy and the morphology in the bone-marrow smear was innocuous, with no sign of relapse or secondary leukemia...
July 1, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28663579/genetic-deletion-or-small-molecule-inhibition-of-the-arginine-methyltransferase-prmt5-exhibit-anti-tumoral-activity-in-mouse-models-of-mll-rearranged-aml
#15
S Kaushik, F Liu, K Veazey, G Gao, P Das, L Neves, K Li, Y Zhong, Y Lu, V Giuliani, M T Bedford, S D Nimer, M A Santos
The hematological malignancies classified as Mixed Lineage leukemias (MLL) harbor fusions of the MLL1 gene to partners that are members of transcriptional elongation complexes. MLL-rearranged leukemias are associated with extremely poor prognosis and response to conventional therapies and efforts to identify molecular targets are urgently needed. Using mouse models of MLL-rearranged acute myeloid leukemia (AML), here we show that genetic inactivation or small molecule inhibition of the protein arginine methyltransferase PRMT5 exhibit anti-tumoral activity in MLL-fusion protein driven transformation...
June 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28658145/central-hypothyroidism-in-a-pediatric-case-of-primary-acute-monoblastic-leukemia-with-central-nervous-system-infiltration-a-case-report
#16
Yuya Sato, Satomi Koyama, Shigeko Kuwashima, Masaya Kato, Mayuko Okuya, Keitaro Fukushima, Hidemitsu Kurosawa, Osamu Arisaka
RATIONALE: Central nervous system (CNS) leukemia is a frequent diagnosis in pediatric acute myeloblastic leukemia (AML) and includes neural symptoms. However, CNS leukemia is rarely associated with central hypsothyroidism. PATIENT CONCERNS AND DIAGNOSES: A 2-year-old female with AML with MLL rearrangement presented with CNS infiltration. Laboratory tests suggested the presence of central hypothyroidism (thyroid-stimulating hormone [TSH]: 0.48 mIU/ml, normal range 0...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28653617/replication-study-inhibition-of-bet-recruitment-to-chromatin-as-an-effective-treatment-for-mll-fusion-leukaemia
#17
Xiaochuan Shan, Juan Jose Fung, Alan Kosaka, Gwenn Danet-Desnoyers
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Fung et al., 2015), that described how we intended to replicate selected experiments from the paper "Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia" (Dawson et al., 2011). Here, we report the results of those experiments. We found treatment of MLL-fusion leukaemia cells (MV4;11 cell line) with the BET bromodomain inhibitor I-BET151 resulted in selective growth inhibition, whereas treatment of leukaemia cells harboring a different oncogenic driver (K-562 cell line) did not result in selective growth inhibition; this is similar to the findings reported in the original study (Figure 2A and Supplementary Figure 11A,B; Dawson et al...
June 27, 2017: ELife
https://www.readbyqxmd.com/read/28650479/aml1-eto-requires-enhanced-c-d-box-snorna-rnp-formation-to-induce-self-renewal-and-leukaemia
#18
Fengbiao Zhou, Yi Liu, Christian Rohde, Cornelius Pauli, Dennis Gerloff, Marcel Köhn, Danny Misiak, Nicole Bäumer, Chunhong Cui, Stefanie Göllner, Thomas Oellerich, Hubert Serve, Maria-Paz Garcia-Cuellar, Robert Slany, Jaroslaw P Maciejewski, Bartlomiej Przychodzen, Barbara Seliger, Hans-Ulrich Klein, Christoph Bartenhagen, Wolfgang E Berdel, Martin Dugas, Makoto Mark Taketo, Daneyal Farouq, Schraga Schwartz, Aviv Regev, Josée Hébert, Guy Sauvageau, Caroline Pabst, Stefan Hüttelmaier, Carsten Müller-Tidow
Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2'-O-methylation as critical determinants of leukaemic stem cell activity. Leukaemogenesis by AML1-ETO required expression of the groucho-related amino-terminal enhancer of split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, global loss of C/D box snoRNAs with concomitant loss of rRNA 2'-O-methylation resulted in decreased leukaemia self-renewal potential...
June 26, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28646646/antileukemic-activity-and-cellular-effects-of-the-antimalarial-agent-artesunate-in-acute-myeloid-leukemia
#19
Bijender Kumar, Arjun Kalvala, Su Chu, Steven Rosen, Stephen J Forman, Guido Marcucci, Ching-Cheng Chen, Vinod Pullarkat
The artimisinins are a class of antimalarial compounds whose antiparasitic activity is mediated by induction of reactive oxygen species (ROS). Herein, we report that among the artimisinins, artesunate (ARTS), an orally bioavailable compound has the most potent antileukemic activity in AML models and primary patients' blasts. ARTS was most cytotoxic to the FLT3-ITD+ AML MV4-11 and MOLM-13 cells (IC50 values of 1.1 and 0.82μM respectively), inhibited colony formation in primary AML and MDS cells and augmented cytotoxicity of chemotherapeutics...
May 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28646565/complete-molecular-remission-in-relapsed-and-refractory-acute-myeloid-leukaemia-with-mll-af9-treated-with-chidamide-based-chemotherapy
#20
Y Lun, J-J Yang, Y Wu
WHAT IS KNOWN AND OBJECTIVE: The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. CASE DESCRIPTION: We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy...
June 23, 2017: Journal of Clinical Pharmacy and Therapeutics
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