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JOURNAL ARTICLE
Guangrong Qin, Jin Dai, Sylvia Chien, Timothy J Martins, Brenda Loera, Quy H Nguyen, Melanie L Oakes, Bahar Tercan, Boris Aguilar, Lauren Hagen, Jeannine McCune, Richard Gelinas, Raymond J Monnat, Ilya Shmulevich, Pamela S Becker
PURPOSE: The inherent genetic heterogeneity of acute myeloid leukemia (AML) has challenged the development of precise and effective therapies. The objective of this study was to elucidate the genomic basis of drug resistance or sensitivity, identify signatures for drug response prediction, and provide resources to the research community. EXPERIMENTAL DESIGN: We performed targeted sequencing, high-throughput drug screening, and single-cell genomic profiling on leukemia cell samples derived from patients with AML...
April 15, 2024: Clinical Cancer Research
#22
JOURNAL ARTICLE
Yong-Xin Ru, Shu-Xu Dong, Jing Liu, Jin-Hua Liu, Yuan Zhou, Brian Eyden
The endoplasmic reticulum（ER）is the largest membranous network serving as a region for protein, lipid and steroid synthesis, transport and storage. Detailed information about ER-cisternae, ER-tubules and rough endoplasmic reticulum (rER) is scarce in human blood cells. This study describes a series of giant inclusions and Auer bodies in promyeloblasts in six patients with acute promyelocytic leukemia (APL), by light microscopy, transmission electron microscopy (TEM) and cytochemical stains. TEM revealed that giant inclusions and pro-Auer bodies were associated with rER and surrounded by tubular structures composed of degenerated or redundant membrane in promyeloblasts, which corresponded with elements of the ER system...
April 15, 2024: Ultrastructural Pathology
#23
JOURNAL ARTICLE
Tobias Suske, Helena Sorger, Gabriele Manhart, Frank Ruge, Nicole Prutsch, Mark W Zimmerman, Thomas Eder, Diaaeldin I Abdallah, Barbara Maurer, Christina Wagner, Susann Schönefeldt, Katrin Spirk, Alexander Pichler, Tea Pemovska, Carmen Schweicker, Daniel Pölöske, Emina Hubanic, Dennis Jungherz, Tony Andreas Müller, Myint Myat Khine Aung, Anna Orlova, Ha Thi Thanh Pham, Kerstin Zimmel, Thomas Krausgruber, Christoph Bock, Mathias Müller, Maik Dahlhoff, Auke Boersma, Thomas Rülicke, Roman Fleck, Elvin Dominic de Araujo, Patrick Thomas Gunning, Tero Aittokallio, Satu Mustjoki, Takaomi Sanda, Sylvia Hartmann, Florian Grebien, Gregor Hoermann, Torsten Haferlach, Philipp Bernhard Staber, Heidi Anne Neubauer, Alfred Thomas Look, Marco Herling, Richard Moriggl
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T cell cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent and clinically challenging STAT5BN642H driver in T cell development and immature T cell cancer onset and compared it with STAT5A hyperactive variants in transgenic mice. Enhanced STAT5 activity caused disrupted T cell development and promoted an early T cell progenitor-ALL phenotype, with upregulation of genes involved in T cell receptor (TCR) signaling, even in absence of surface TCR...
April 15, 2024: Journal of Clinical Investigation
#24
JOURNAL ARTICLE
Yogen Saunthararajah
Cell and antibody therapies directed against surface molecules on B cells, e.g., CD19-targeting chimeric antigen receptor T cells (CD19 CAR-T), are now standard for patients with chemorefractory B cell acute lymphoblastic leukemias and other B cell malignancies. However, early relapse rates remain high. In this issue of the JCI, Aminov, Giricz, and colleagues revealed that leukemia cells resisting CD19-targeted therapy had reduced CD19 but also low CD22 expression and were sensitive to Bruton's tyrosine kinase and/or MEK inhibition...
April 15, 2024: Journal of Clinical Investigation
#25
JOURNAL ARTICLE
Agata Gruszczynska, Abhishek Maiti, Christopher A Miller, Sai Mukund Ramakrishnan, Daniel C Link, Geoffrey L Uy, Allegra A Petti, Kala Hayes, Courtney D DiNardo, Farhad Ravandi, Timothy J Ley, David H Spencer, Feng Gao, Marina Y Konopleva, John S Welch
Not available.
April 11, 2024: Haematologica
#26
JOURNAL ARTICLE
Waad Almuatasem Mohieldeen, Albara Ahmed, Yousif Mohammed Elmosaad, Rania Saad Suliman, Abdulaziz Alfahed, Ahmed Hjazi, Humood Al Shmrany, Nora Hakami, Mohammed Ageeli Hakami, Alhomidi Almotiri, Hisham Ali Waggiallah
BACKGROUND: A genetic polymorphism that causes abnormal folate metabolism may lead to genomic instability and increase susceptibility to malignancies such as Acute Lymphoblastic leukemia (ALL). The purpose of this research is to identify methylene tetrahydrofolate reductase (MTHFR C677T) (NCBI ID: 4524) mutation in ALL patients. METHODS: The study was a descriptive case-control hospital-based study with one hundred Sudanese participants divided equally into fifty (50) Sudanese ALL diagnosed patients as cases and fifty (50) Sudanese individuals as controls...
October 2023: Reports of Biochemistry & Molecular Biology
#27
JOURNAL ARTICLE
Bader B Alsulays, Alhussain H Aodah, Mohammad Muqtader Ahmed, Md Khalid Anwer
PURPOSE: Ivosidenib (IVO), an isocitrate dehydrogenase-1 (IDH1) used for treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. However, poor solubility, low bioavailability, high dose and side effects limit clinical application of IVO. METHODS: Ivosidenib-loaded PLGA nanoparticles (IVO-PLGA-NPs) and Ivosidenib-loaded chitosan coated PLGA nanoparticles (IVO-CS-PLGA-NPs) were prepared using emulsification and solvent evaporation method for the treatment of liver cancer...
2024: International Journal of Nanomedicine
#28
JOURNAL ARTICLE
Sanila Sarkar, Lea M Stitzlein, Joya Chandra
Electronic cigarettes, which deliver an aerosolized, nicotine-containing product upon inhalation, are a public health issue that continue to gain popularity among adolescents and young adults in the United States. Use of electronic cigarettes is wide, and extends to pediatric patients with multiple comorbidities, including childhood cancer, leaving them vulnerable to further negative health outcomes. Acute leukemias are the most common type of cancer in pediatric populations, and treatment outcomes for these patients are improving; consequently, there is an increased emphasis on the effect of behavioral lifestyle factors on quality of life in survivorship...
February 28, 2024: Pediatric medicine
#29
JOURNAL ARTICLE
Dristhi Ragoonanan, Hisham Abdel-Azim, Aditya Sharma, Saleh Bhar, Jennifer McArthur, Renee Madden, April Rahrig, Rajinder Bajwa, Jian Wang, Victoria Sun, Mariah Wright, Rebekah Lassiter, Basirat Shoberu, Jitesh Kawedia, Sajad Jawad Khazal, Kris Michael Mahadeo
BACKGROUND: Sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic cell transplantation, high-intensity chemotherapies and increasingly seen with calicheamicin based leukemia therapies. Paediatric specific European Society for Blood and Marrow Transplantation (pEBMT) diagnostic criteria have demonstrated benefit in single center studies compared to historic criteria. Yet, the extent to which they have been universally implemented remains unclear. METHODS: We conducted a retrospective multi-centre study to examine the potential impact of the Baltimore, modified Seattle and pEBMT criteria on the incidence, severity, and outcomes of sinusoidal obstruction syndrome among paediatric hematopoietic cell transplantation patients...
May 2024: Lancet Reg Health Am
#30
JOURNAL ARTICLE
Uri Greenbaum, Dana Yehudai-Ofir, Ofrat Beyar Katz, Liat Shargian, Elad Jacoby, Sigal Grisaru, Tsila Zuckerman, Ron Ram, Abraham Avigdor
Using immunotherapy to fight cancer, and specifically, the use of engineered T-cells expressing a chimeric receptor against an antigen found on malignant cells (chimeric antigen receptor, CAR-T cells) constitutes a significant breakthrough in the treatment of the disease. In recent years, several CAR-T therapies have been approved in Europe and the USA, and some are already approved and funded through the national health basket in Israel, for the indications of diffuse large B-cell lymphoma, mantle cell lymphoma and B-cell acute lymphoblastic leukemia, after the failure of at least two lines of treatment...
April 2024: Harefuah
#31
JOURNAL ARTICLE
Juliette Renaud, Bianca F Goemans, Franco Locatelli, Martina Pigazzi, Shelagh Redmond, Claudia E Kuehni, Alice Destaillats, Todd A Alonzo, Robert B Gerbing, Alan Gamis, Richard Aplenc, Raffaele Renella, Todd Cooper, Francesco Ceppi
BACKGROUND: Myeloid neoplasms account for 50% of cases of pediatric leukemias in infants. Approximately 25%-50% of patients with newborn leukemia have cutaneous extramedullary disease (EMD). In less than 10% of patients, aleukemic leukemia cutis or isolated extramedullary disease with cutaneous involvement (cEMD) occurs when skin lesions appear prior to bone marrow involvement and systemic symptoms. Interestingly, in acute myeloid leukemia with cutaneous EMD (AML-cEMD) and cEMD, spontaneous remissions have been reported...
April 14, 2024: Pediatric Blood & Cancer
#32
JOURNAL ARTICLE
Yizhou Peng, Jinjin Huang, Jin Yin, Fankai Meng, Yang Cao, Liang Huang, Dengju Li, Yicheng Zhang, Donghua Zhang, Li Meng, Zhiqiang Han, Zhenya Hong
BACKGROUND: Studies on dasatinib-based low-intensity induction regimens and post-remission strategies are limited in China. Therefore, we conducted a single-center phase 2 trial in newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) to establish the efficacy and safety of this treatment approach. RESEARCH DESIGN AND METHODS: Patients received one month of dasatinib plus low-intensity chemotherapy and two months of dasatinib monotherapy for induction, followed by a single course of high-dose methotrexate for consolidation...
April 14, 2024: Expert Review of Hematology
#33
REVIEW
Qiangan Jing, Chaoting Zhou, Junyu Zhang, Ping Zhang, Yunyi Wu, Junyu Zhou, Xiangmin Tong, Yanchun Li, Jing Du, Ying Wang
Reactive oxygen species (ROS) serve as typical metabolic byproducts of aerobic life and play a pivotal role in redox reactions and signal transduction pathways. Contingent upon their concentration, ROS production not only initiates or stimulates tumorigenesis but also causes oxidative stress (OS) and triggers cellular apoptosis. Mounting literature supports the view that ROS are closely interwoven with the pathogenesis of a cluster of diseases, particularly those involving cell proliferation and differentiation, such as myelodysplastic syndromes (MDS) and chronic/acute myeloid leukemia (CML/AML)...
April 14, 2024: Cellular & Molecular Biology Letters
#34
JOURNAL ARTICLE
Xinghao Yu, Yiyin Chen, Jia Chen, Yi Fan, Huimin Lu, Depei Wu, Yang Xu
BACKGROUND: To study the shared genetic structure between autoimmune diseases and B-cell acute lymphoblastic leukemia (B-ALL) and identify the shared risk loci and genes and genetic mechanisms involved. METHODS: Based on large-scale genome-wide association study (GWAS) summary-level data sets, we observed genetic overlaps between autoimmune diseases and B-ALL, and cross-trait pleiotropic analysis was performed to detect shared pleiotropic loci and genes. A series of functional annotation and tissue-specific analysis were performed to determine the influence of pleiotropic genes...
April 15, 2024: BMC Medicine
#35
REVIEW
Hee Sue Park
Recently, the International Consensus Classification (ICC) and the 5th edition of the World Health Organization classification (WHO2022) introduced diagnostically similar yet distinct approaches, which has resulted in practical confusion. This review compares these classification systems for acute myeloid leukemia (AML), building up on the revised 4th edition of WHO (WHO2016). Both classifications retain recurrent genetic abnormalities as a primary consideration. However, they differ in terms of blast threshold...
April 15, 2024: Blood Research
#36
JOURNAL ARTICLE
Shiyi Pan, Qinghua Cai, Yiqiong Wei, Haifeng Tang, Yuping Zhang, Wei Zhou, Tingfen Deng, Wenjian Mo, Shunqing Wang, Caixia Wang, Cunte Chen
BACKGROUND: Inducible co-stimulatory factor (ICOS) has a dual role: activating cytotoxic T cells against tumors or exacerbating immunosuppression of regulatory T cells (Tregs) to participate in immune evasion. However, the correlation between ICOS and its co-expression with inhibitory immune checkpoints (IICs) and prognosis in acute myeloid leukemia (AML) is little known. METHODS: The prognostic importance of ICOS and IICs in 62 bone marrow (BM) samples of de novo AML patients from our clinical center (GZFPH) was explored and then the RNA sequencing data of 155 AML patients from the Cancer Genome Atlas (TCGA) database was used for validation...
April 11, 2024: Immunobiology
#37
JOURNAL ARTICLE
Arnon Nagler, Myriam Labopin, Ryszard Swoboda, Thomas Schroeder, Rose-Marie Hamladji, Laimonas Griskevicius, Urpu Salmenniemi, Alessandro Rambaldi, Stephan Mielke, Alexander Kulagin, Jakob Passweg, Thomas Luft, Tobias Gedde-Dahl, Edouard Forcade, Grzegorz Helbig, Matthias Stelljes, Cristina Castilla-Llorente, Alexandros Spyridonidis, Eolia Brissot, Fabio Ciceri, Mohamad Mohty
Post-transplant cyclophosphamide plus calcineurin inhibitor (CNI)(tacrolimus or cyclosporine A) plus mycophenolate mofetil (PTCy/TAC or CSA/MMF) and anti-thymocyte globulin plus CNI (tacrolimus or cyclosporine A) plus methotrexate (ATG/TAC or CSA/MTX) are common graft-versus-host disease (GVHD) prophylaxis regimens. We compared the two regimens in patients with acute myeloid leukemia (AML) undergoing allogeneic transplantation from matched siblings or unrelated donors. 402 received PTCy/TAC or CSA/MMF and 5648 received ATG/TAC or CSA/MTX...
April 13, 2024: Bone Marrow Transplantation
#38
Adrianna Spałek, Aleksandra Bartkowska-Chrobok, Marta Kulińska-Kozak, Bożena Szymczak, Joanna Dziaczkowska-Suszek, Grzegorz Helbig
No abstract text is available yet for this article.
April 1, 2024: Hematology, Transfusion and Cell Therapy
#39
JOURNAL ARTICLE
Bella Madan, Margareth C Ozelo, Priyanka Raheja, Emily Symington, Doris V Quon, Andrew D Leavitt, Steven W Pipe, Gillian Lowe, Gili Kenet, Mark T Reding, Jane Mason, Michael Wang, Annette von Drygalski, Robert Klamroth, Susan Shapiro, Hervé Chambost, Amy L Dunn, Johannes Oldenburg, Sheng-Chieh Chou, Flora Peyvandi, Carolyn M Millar, Dane Osmond, Hua Yu, Ebony Dashiell-Aje, Tara M Robinson, Johnny Mahlangu
BACKGROUND: Valoctocogene roxaparvovec transfers a human factor VIII (FVIII) coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection. OBJECTIVE: Present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial. METHODS: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis. Efficacy endpoints included annualized bleeding rate (ABR), annualized FVIII utilization (AFU), FVIII activity (chromogenic substrate assay; imputed as 1 IU/dL at baseline and 0 IU/dL after discontinuation), and the Haemophilia-Specific Quality of Life Questionnaire for Adults (Haemo-QOL-A)...
April 11, 2024: Journal of Thrombosis and Haemostasis: JTH
#40
JOURNAL ARTICLE
Mio Matsumoto, Momoko Oyake, Tomoyo Itonaga, Miwako Maeda, Soichi Suenobu, Daichi Satob, Yoji Sasahara, Hiroyuki Mishima, Koh-Ichiro Yoshiura, Kenji Ihara
ADH5/ALDH2 deficiency is a rare inherited syndrome characterized by short stature, microcephaly, delayed mental development, and hematopoietic dysfunction and has recently been proposed as a disease paradigm. Acute and severe presentations include aplastic anemia, myelodysplastic syndrome, or leukemia, requiring bone marrow transplantation during childhood. Conversely, non-hematological manifestations may exhibit a prolonged and nonspecific clinical trajectory, with growth failure and developmental delay, most of which are often overlooked, particularly in patients with milder symptoms...
April 11, 2024: European Journal of Medical Genetics
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