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Acute Myelogenic Leukemia

Yahui Ding, Wenwei Pan, Junqing Xu, Tianpeng Wang, Tianyang Chen, Zhongquan Liu, Chunfeng Xie, Quan Zhang
One new eudesmane sesquiterpenoid, 11β-hydroxy-13-chloro-eudesm-5-en-12, 8-olide (1), was isolated from the roots of Inula helenium together with nine eudesmanolides (2-10) and one germacranolide (11). Their structures were elucidated on the basis of detailed spectroscopic analyses. All isolates were evaluated for their antiproliferative activities against human leukemia stem-like cell line KG1a. Compound 10 exhibited the most potent effect with the IC50 value of 3.36 ± 0.18 μM. A further investigation revealed that compound 10 could significantly induce apoptosis of KG1a cells...
January 31, 2019: Bioorganic Chemistry
Angela Wipf, Heidi Wipf, Daniel Miller
Pseudocarcinomatous (pseudoepitheliomatous) hyperplasia represents reactive epidermal change mimicking squamous cell carcinoma (SCC), owing to a variety of inflammatory and neoplastic phenomena, including deep fungal infections, CD30-positive lymphomas, and others. We report a case of Sweet syndrome (SS) arising in a patient with acute myelogenous leukemia, with persistent orolabial involvement which mimicked SCC both clinically and microscopically, but resolved entirely with adequate corticosteroid treatment...
February 7, 2019: Journal of Cutaneous Pathology
Fang Dong, Haitao Bai, Xiaofang Wang, Shanshan Zhang, Zhao Wang, Miner Xie, Sen Zhang, Jinhong Wang, Sha Hao, Tao Cheng, Hideo Ema
The cell of origin, defined as the normal cell in which the transformation event first occurs, is poorly identified in leukemia, despite its importance in understanding of leukemogenesis and improving leukemia therapy. Although hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were used for leukemia models, whether their self-renewal and differentiation potentials influence the initiation and development of leukemia is largely unknown. In this study, the self-renewal and differentiation potentials in 2 distinct types of HSCs (HSC1 [CD150+ CD41- CD34- Lineage- Sca-1+ c-Kit+ cells] and HSC2 [CD150- CD41- CD34- Lineage- Sca-1+ c-Kit+ cells]) and 3 distinct types of HPCs (HPC1 [CD150+ CD41+ CD34- Lineage- Sca-1+ c-Kit+ cells], HPC2 [CD150+ CD41+ CD34+ Lineage- Sca-1+ c-Kit+ cells], and HPC3 [CD150- CD41- CD34+ Lineage- Sca-1+ c-Kit+ cells]) were isolated from adult mouse bone marrow, and examined by competitive repopulation assay...
February 12, 2019: Blood Advances
Jill A Bell, Aaron Galaznik, Eileen Farrelly, Marlo Blazer, Sharanya Murty, Augustina Ogbonnaya, Michael Eaddy, Robert J Fram, Douglas V Faller, Vamsi K Kota
Intensive treatment for newly diagnosed acute myelogenous leukemia (ND-AML) patients are reserved for "fit" patients. While guidelines recommend evaluation of age, performance status and comorbidities, there is no consensus on the definition of "fitness" or optimal therapy for elderly AML patients. This retrospective study evaluated characteristics and survival outcomes of 274 patients (age ≥60 years) with ND-AML treated with 7 + 3 (cytarabine + an anthracycline) vs. hypomethylating agents (HMAs)...
March 2019: Leukemia Research
Dandan Wang, Weijie Zhou, Jingyu Chen, Wei Wei
Phosphoinositide 3-kinase (PI3K), a crucial signaling molecule, is regulated by various upstream regulators. Traditionally, receptor tyrosine kinases and G protein-coupled receptor are regarded as its principle upstream regulators; however, recent reports have indicated that spleen tyrosine kinase, β-arrestin2, Janus kinase, and RAS can also perform this role. Dysregulation of PI3K is common in the progression of various diseases, including, but not limited to, tumors, Alzheimer's disease, Parkinson's disease, rheumatoid arthritis, and acute myelogenous leukemia...
February 2, 2019: Journal of Cellular Physiology
Yuan-Yuan Zhang, Xiao-Dong Mo, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Yu-Qian Sun, Kai-Yan Liu, Xiao-Jun Huang
Acute myelogenous leukemia (AML) patients with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) have poor prognoses if treated with chemotherapy only, primarily as they experience increased relapse rates. To determine whether this alteration also affects outcomes after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT), we compared 334 consecutive FLT3-ITD-positive vs -negative patients with AML (other than acute promyelocytic leukemia) who underwent HID-HSCT...
February 1, 2019: Bone Marrow Transplantation
Z X Chen
No abstract text is available yet for this article.
January 14, 2019: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Naxin Guo, Mitra Azadniv, Myra Coppage, Mary Nemer, Jason Mendler, Michael Becker, Jane Liesveld
Acute myelogenous leukemia (AML) is a heterogeneous disease and often relapses after standard chemotherapy. Recently, the neddylation (NEDD8) and the mammalian target of rapamycin (mTOR) signaling pathways have emerged as promising pharmaceutical targets for AML therapy. However, the interaction of these two pathways remains unclear. Here we evaluated the effects of pevonedistat, an inhibitor of the NEDD8 activating enzyme (NAE), and sapanisertib (TAK-228), an inhibitor of mTORC1 and mTORC2 as single agents or in combination on AML cell lines...
January 27, 2019: Translational Oncology
Yllka Latifi, Federico Moccetti, Melinda Wu, Aris Xie, William Packwood, Yue Qi, Koya Ozawa, Weihui Shentu, Eran Brown, Toshiaki Shirai, Owen J McCarty, Zaverio Ruggeri, Javid Moslehi, Junmei Chen, Brian J Druker, Jose A López, Jonathan R Lindner
The third generation tyrosine kinase inhibitor (TKI) ponatinib is effective against drug-resistant chronic myelogenous leukemia, but has been plagued by high rates of acute ischemic events. The pathophysiology responsible for these events is unknown. We hypothesized that ponatinib produces an endothelial angiopathy involving excessive endothelial-associated von Willebrand factor (VWF) and secondary platelet adhesion. In wild-type mice and ApoE-/- mice on Western diet, contrast-enhanced ultrasound molecular imaging of the thoracic aorta for VWF A1-domain and glycoprotein-Ibα was performed to quantify endothelial-associated VWF and platelet adhesion...
January 28, 2019: Blood
Xin-Jie Chen, Wei-Na Zhang, Bing Chen, Wen-Da Xi, Ying Lu, Jin-Yan Huang, Yue-Ying Wang, Jun Long, Song-Fang Wu, Yun-Xiang Zhang, Shu Wang, Si-Xing Li, Tong Yin, Min Lu, Xiao-Dong Xi, Jun-Min Li, Kan-Kan Wang, Zhu Chen, Sai-Juan Chen
Homoharringtonine (HHT), a known protein synthesis inhibitor, has an anti-myeloid leukemia effect and potentiates the therapeutic efficacy of anthracycline/cytarabine induction regimens for acute myelogenous leukemia (AML) with favorable and intermediate prognoses, especially in the t(8;21) subtype. Here we provide evidence showing that HHT inhibits the activity of leukemia-initiating cells (Lin- /Sca-1- /c-kit+ ; LICs) in a t(8;21) murine leukemia model and exerts a down-regulating effect on MYC pathway genes in human t(8;21) leukemia cells (Kasumi-1)...
January 18, 2019: Proceedings of the National Academy of Sciences of the United States of America
Sarah A McGuffin, Rajnish Bharadwaj, Luis F Gonzalez-Cuyar, Joshua T Schiffer, Andrew W Stacey, Roland B Walter, Elizabeth R Duke
No abstract text is available yet for this article.
January 18, 2019: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Jing-Wen Zhang, Xiang-Zhong Zhang, Yan-Ling Sun, Bing Long, Xiao-Zhen Wang, Xu-Dong Li
BACKGROUND: After allogeneic haematopoietic stem cell transplantation (allo-HSCT), Hepatitis B virus reactivation (HBVr) can be observed in patients with previous resolved Hepatitis B virus (HBV) infections. Nephrotic syndrome (NS) is the main clinical manifestation of HBsAg-positive glomerulonephritis. However, the development of HBVr combined with NS after allo-HSCT is uncommon. CASE PRESENTATION: We presented a case of a 47-year-old female with acute myelogenous leukemia who underwent HLA-identical sibling allo-HSCT and achieved leukemia free survival...
January 16, 2019: BMC Infectious Diseases
Ivar S Jensen, Elizabeth Wu, Naomi C Sacks, Philip L Cyr, Karen C Chung
Background: Current national estimates for acute myelogenous leukemia (AML) indicate this disease accounts for 1.1% of new cancer diagnoses and 1.8% of cancer deaths in the United States. The 5-year overall survival rate for patients with AML was 27.4% between 2008 and 2014. The standard induction for patients with AML includes cytarabine, infused for 7 days, with 3 once-daily injections of an anthracycline, such as daunorubicin, known as the 7+3 regimen. Daunorubicin plus cytarabine liposomal encapsulation for injection was approved in the United States in 2017 for adults with newly diagnosed therapy-related AML (tAML) or AML with myelodysplasia-related changes (AML-MRC)...
October 2018: American Health & Drug Benefits
Tiffany J Libby, Kirsten Fleming, Bijal Amin
Histiocytoid Sweet syndrome (HSS) is a rare histopathologic variant of Sweet syndrome that was first described in 2005 by Requena et al. In contrast to the dense infiltrate of mature neutrophils seen in conventional Sweet syndrome, this variant demonstrates dermal and/or subcutaneous infiltrate with a prominent component of immature myeloid cells resembling histiocytes. (1) A number of publications have since reported similar findings, sometimes in association with hematologic neoplasms. In recent years, an ever increasing number of mutations have been discovered in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), including mutations in isocitrate dehydrogenase 1 (IDH-1) and isocitrate dehydrogenase 2 (IDH-2)...
January 10, 2019: Journal of Cutaneous Pathology
Clémence Lepelletier, Jean-David Bouaziz, Michel Rybojad, Martine Bagot, Sophie Georgin-Lavialle, Marie-Dominique Vignon-Pennamen
Neutrophilic dermatoses (ND) are a group of conditions characterized by an aseptic accumulation of polymorphonuclear leukocytes in the skin. Occurrence of ND in association with myeloid malignancies, mainly myelodysplastic syndrome and myelogenous acute leukemia, is not rare and is often associated with a poor prognosis. Recent findings have improved understanding of the pathophysiology of myeloid malignancy-associated ND. We review the clinical spectrum of myeloid malignancy-associated ND with an emphasis on recently identified mechanisms...
January 10, 2019: American Journal of Clinical Dermatology
Limin Liu, Xingxia Zhang, Huiying Qiu, Xiaowen Tang, Yue Han, Chengcheng Fu, Zhengming Jin, Mingqing Zhu, Miao Miao, Depei Wu
HLA-mismatched stem cell microtransplantation is a new form of transplantation reported in recent years. We compared 59 patients undergoing microtransplantation to 66 patients undergoing HLA-matched sibling donor (MSD) transplantation at the same period from April 2012 to December 2016, who all suffered from intermediate/high-risk acute myelogenous leukemia (AML) in first complete remission (CR1). The estimated overall survival (OS) at 2 years was 74.1% ± 6.2% and 34.3% ± 7.9% in MSD and microtransplantation group, respectively (P = 0...
January 10, 2019: Annals of Hematology
Hidenori Kunou, Ryu Kanzaki, Tomohiro Kawamura, Takashi Kanou, Naoko Ose, Soichiro Funaki, Yasushi Shintani, Masato Minami, Meinoshin Okumura
Air leak syndrome (ALS) is a rare complication after bone marrow transplantation (BMT) and usually has a fatal outcome because of the high recurrence rate and treatment-refractory nature. A 32-year-old man with a history of BMT for acute lymphoblastic leukemia suffered from metachronous bilateral ALS. Bullectomy and the pleural covering procedure (PLC) were successfully performed for each side of the thorax. After surgery, no relapse of pneumothorax was seen for 2 years on the right side and for 1 year on the left side...
January 2, 2019: General Thoracic and Cardiovascular Surgery
Jing Lu, Yu-Hang Zhang, ShaoPeng Wang, Yi Bi, Tao Huang, Xiaomin Luo, Yu-Dong Cai
AIM AND OBJECTIVE: Leukemia is the second common blood cancer after lymphoma, and its incidence rate has an increasing trend in recent years. Leukemia can be classified into four types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML). More than forty drugs are applicable for different types of leukemia based on the discrepant pathogenesis. Therefore, the identification of specific drug-targeted biological processes and pathways is helpful to determinate the underlying pathogenesis among such four types of leukemia...
December 31, 2018: Combinatorial Chemistry & High Throughput Screening
Josip Skoko, Jan Rožanc, Emilie M Charles, Leonidas G Alexopoulos, Markus Rehm
BACKGROUND: Dasatinib (Sprycel) was developed as a tyrosine kinase inhibitor targeting Bcr-Abl and the family of Src kinases. Dasatinib is commonly used for the treatment of acute lymphoblastic and chronic myelogenous leukemia. Previous clinical studies in melanoma returned inconclusive results and suggested that patients respond highly heterogeneously to dasatinib as single agent or in combination with standard-of-care chemotherapeutic dacarbazine. Reliable biomarkers to predict dasatinib responsiveness in melanoma have not yet been developed...
December 27, 2018: BMC Cell Biology
Guangle Song, Leiying Yang
OBJECTIVE: To investigate the effect of targeted inhibition of CD47 gene expression on stem cell clearance in acute myeloid leukemia. METHODS: After the lentiviral CD47-siRNA was transfected into acute myelogenous leukemia stem cells (LSCs), the proliferative status of acute myelogenous LSCs was detected by cell counting kit-8, and the apoptosis of stem cells of acute myeloid leukemia was detected by annexin/propidium iodide flow assays. The expression of Bcl-2, Bcl-xl, MCL-1, PIK3p110β, and interleukin (IL)-3 in acute myeloid LSCs was detected by Western blot analysis and the activity of protein phosphatase 2A (PP2A) and the protein content of CD96 and CD90 were measured by enzyme-linked immunosorbent assay kits...
December 19, 2018: Journal of Cellular Biochemistry
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