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AML Treatment

Zengqian Hui, Zhao Liu, Aili He, Yinxia Chen, Pengyu Zhang, Bo Lei, Huan Yao, Yong Yu, Rui Liang, Zhanning Li, Wanggang Zhang
Understanding the mechanisms of malignancy in acute myeloid leukemia (AML) cell is important for the targeted treatment and drug development. We found that visfatin, a 52-kDa adipokine, can positively regulate the proliferation of AML cells. Targeted inhibition of visfatin via its specific siRNAs or inhibitor can suppress the proliferation of AML cells. Further, knockdown of visfatin can increase the doxorubicin (Dox) and cisplatin (CDDP) sensitivity of AML cells. Among the tested six cytokines, si-visfatin can decrease the expression of interleukin-17 (IL-17)...
March 12, 2019: European Journal of Pharmacology
Zachariah Payne Sellers, Lukasz Bolkun, Janusz Kloczko, Marzena Liliana Wojtaszewska, Krzysztof Lewandowski, Marcin Moniuszko, Mariusz Z Ratajczak, Gabriela Schneider
BACKGROUND: The delta-like non-canonical Notch ligand 1 (DLK1)-maternally expressed 3(MEG3) locus (DLK1-MEG3 locus) plays a critical role in the maintenance and differentiation of hematopoietic stem cells. Accumulating evidence implicates the imprinted genes from this locus, DLK1 and MEG3, in the development and progression of acute myeloid leukemia (AML). However, the contribution of this locus to the treatment response of patients and their survival is unknown. METHODS: DNA methylation of select CG dinucleotide-containing amplicons (CpG sites) within the DLK1-MEG3 locus and within differentially methylated regions of other imprinted loci was assessed in the mononuclear cells of 45 AML patients by combined bisulfite restriction analysis...
March 15, 2019: Clinical Epigenetics
Anne Stidsholt Roug, Hans Beier Ommen
Treatment of acute myeloid leukemia (AML) remains a high-risk venture for the patient suffering from the disease. There is a real risk of succumbing to the treatment rather than the disease, and even so, cure is much less than certain. Since the establishment of complete remission as a prerequisite for cure in the 1960s, a number of years passed before advanced techniques for detecting minute amounts of disease matured sufficiently for clinical implementation. The two main techniques for detection of measurable residual disease (MRD) remain qPCR and multicolor flow cytometry...
March 14, 2019: Current Treatment Options in Oncology
Jannick Theobald, Mohamed A Abu El Maaty, Nico Kusterer, Bernhard Wetterauer, Michael Wink, Xinlai Cheng, Stefan Wölfl
Organ-on-chip platforms provide models that allow the representation of human physiological processes in cell-based miniaturized systems. Potential pre-clinical applications include drug testing and toxicity studies. Here we describe the use of a multi-compartment micro-fluidic chip to recapitulate hepatic vitamin D metabolism (vitamin D to 25-hydroxyvitamin D) and renal bio-activation (25-hydroxyvitamin D to 1,25-dihydroxyvitamin D) in humans. In contrast to cultivation in conventional tissue culture settings, on-chip cultivation of HepG2 and RPTEC cells in interconnected chambers, used to mimic the liver and kidneys, respectively, resulted in the enhanced expression of vitamin D metabolizing enzymes (CYP2R1, CYP27B1 and CYP24A1)...
March 15, 2019: Scientific Reports
Peong Gang Park, Che Ry Hong, Eunjeong Kang, Minsu Park, Hajeong Lee, Hyoung Jin Kang, Hee Young Shin, Il-Soo Ha, Hae Il Cheong, Hyung Jin Yoon, Hee Gyung Kang
OBJECTIVE: To analyze the incidence of acute kidney injury (AKI) in the first year after cancer diagnosis in children and to evaluate the short-term and long-term effects on renal function and proteinuria. STUDY DESIGN: Retrospective review of medical records was done on children who were diagnosed and treated for cancer at Seoul National University Hospital between 2004 and 2013. AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria...
March 11, 2019: Journal of Pediatrics
Junji Ikeda, Norio Shiba, Shin-Ichi Tsujimoto, Masanori Yoshida, Kazuhiko Nakabayashi, Hiroko Ogata-Kawata, Kohji Okamura, Masanobu Takeuchi, Tomoo Osumi, Daisuke Tomizawa, Kenichiro Hata, Nobutaka Kiyokawa, Shuichi Ito, Motohiro Kato
Infant acute lymphoblastic leukemia with lysine (K)-specific methyltransferase 2A (KMT2A) rearrangements usually has a poor prognosis regardless of the fusion partners of KMT2A. However, the prognosis of pediatric acute myeloid leukemia (AML) with KMT2A rearrangements depends on its translocation partners. We herein report the case of a 9-month-old boy with a KMT2A-USP2 fusion, which required diagnosis by whole transcriptome sequencing after the failure of detection of known translocation partners by conventional screening approaches...
March 14, 2019: Genes, Chromosomes & Cancer
Adenauer Marinho de Oliveira Góes Junior, Salim Abdon Haber Jeha, Carolina Pinheiro de Oliveira, Daniel Arthur Santos Dos Santos
Angiomyolipomas (AMLs) are rare benign tumors derived from mesenchymal tissue and composed of varying degrees of adipose tissue, muscle and blood vessels. Renal AMLs (RAMLs) are the result of a sporadic event, and, in most of cases, the diagnosis is usually incidental, but hemorrhage and shock may be present. During pregnancy, the size of AMLs may increase and they may rupture, probably due to the high expression of hormone receptors, and the increase in maternal circulation and abdominal pressure. The authors present a case of a woman with ruptured RAML submitted to urgent endovascular treatment four days after giving birth by cesarean section...
March 13, 2019: Revista Brasileira de Ginecologia e Obstetrícia
Suqin Lv, Aihua Li, Haijuan Wu, Xiaoli Wang
Efficacy and toxic and side effects of pirarubicin combined with cytarabine and mitoxantrone combined with cytarabine on the treatment of initially treated acute myeloid leukemia (AML) were compared. A retrospective analysis was performed on the medical records of 76 AML patients who were initially treated in Weifang People's Hospital. Among them, 36 patients (observation group) were treated with pirarubicin combined with cytarabine, and 40 patients (control group) were treated with mitoxantrone combined with cytarabine...
March 2019: Oncology Letters
Nguyen Khoi Song Tran, Goon-Tae Kim, Do Yup Lee, Young-Jun Kim, Hye-Jin Park, Dong Ki Park, Tae-Sik Park
Nonalcoholic fatty liver disease is a progressive disease involving the accumulation of lipid droplets in the liver. In this study, we investigated the anti-hepatosteatosis effects of fermented Cordyceps militaris extract (CME) in AML-12 hepatocytes. Although the levels of adenosine and cordycepin were reduced in the extracts of CM grown on germinated soybean (GSCE) and fermented CM grown on germinated soybean (GSC) by Pediococcus pentosaceus ON188 (ON188E), the expression of fatty acid oxidation (FAO) genes were upregulated only by GSC-ON188E treatment in a dose-dependent manner...
March 13, 2019: Journal of Medicinal Food
Larisa Broglie, Jill Gershan, Michael J Burke
Children with multiple relapsed or refractory leukemia have dismal survival. Research has identified engagement of immune checkpoint receptors (e.g., PD-1, PD-L1 and CTLA-4) as a mechanism for treatment resistance. For adult cancer, inhibitors of PD-1 (nivolumab) and CTLA-4 (ipilimumab) have shown promise with response rates ranging from 7 to 40%. In vitro studies using acute myeloid leukemia cell lines have shown that acute myeloid leukemia blasts may similarly utilize the PD-1/PD-L1 axis to evade an anticancer immune response...
February 2019: International Journal of Hematologic Oncology
Ya-Chen Ko, Chung-Yi Hu, Zheng-Hau Liu, Hwei-Fang Tien, Da-Liang Ou, Hsiung-Fei Chien, Liang-In Lin
Internal tandem duplication of FLT3 juxtamembrane domain (FLT3-ITD)-positive acute myeloid leukemia (AML) leads to poor clinical outcomes after chemotherapy. We aimed to establish a cytarabine-resistant line from FLT3 -ITD-positive MV4-11 (MV4-11-P) cells and examine the development of resistance. The FLT3 -ITD mutation was retained in MV4-11-R; however, the protein was underglycosylated and less phosphorylated in these cells. Moreover, the phosphorylation of ERK1/2, Akt, MEK1/2 and p53 increased in MV4-11-R...
March 11, 2019: International Journal of Molecular Sciences
Ing S Tiong, Andrew H Wei
The therapeutic landscape is rapidly changing, with 8 new drugs approved by the Food and Drug Administration within the last 2 years, including midostaurin and gilteritinib for FLT3 mutant newly diagnosed and relapsed/refractory (R/R) acute myeloid leukemia (AML), respectively; CPX-351 (liposomal cytarabine and daunorubicin) for therapy-related AML and AML with myelodysplasia-related changes; gemtuzumab ozogamicin (anti-CD33 monoclonal antibody conjugated with calicheamicin) for newly diagnosed and R/R CD33-positive AML; enasidenib and ivosidenib for IDH2 and IDH1 mutant R/R AML, respectively...
March 12, 2019: Genes, Chromosomes & Cancer
Sarah Oelsner, Anja Waldmann, Arne Billmeier, Jasmin Röder, Aline Lindner, Evelyn Ullrich, Rolf Marschalek, Gianpietro Dotti, Gundram Jung, Ludger Große-Hovest, Pranav Oberoi, Peter Bader, Winfried S Wels
Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells represent a promising effector cell type for adoptive cancer immunotherapy. Both, genetically modified donor-derived NK cells as well as continuously expanding NK-92 cells are currently under clinical development. To enhance their therapeutic utility for the treatment of pre-B cell acute lymphoblastic leukemia (B-ALL), we engineered NK-92 cells by lentiviral gene transfer to express a FMS-like tyrosine kinase 3 (FLT3)-specific CAR that contains a composite CD28-CD3ζ signaling domain...
March 12, 2019: International Journal of Cancer. Journal International du Cancer
Narjes Mehrvar, Mohammad Esmail Akbari, Mohammad Reza Rezvany, Hasan Abolghasemi, Javad Saberynejad, Azim Mehrvar, Mohammad Faranoush, Ali Asghar Keramatinia, Reza Shekarriz-Foumani, Abolfazl Movafagh
Multidrug resistance based on ABC transporters' gene expression is one of the most important health challenges through chemotherapy of patients. This resistance can cause relapse or treatment failure. The goal of this conducted study was to evaluate the results of published reports which considered ABC transporters' gene expression in pediatric patients with acute leukemia. PubMed as a free search engine was chosen. The following Mesh terms were used as: "ATP-binding cassette transporters" OR "ABC-transporters*" AND "gene expression*" AND "leukemia" OR "ALL" OR "AML" OR "acute leukemia*"...
February 28, 2019: Cellular and Molecular Biology
Yan Li, Jamie N Connarn, Jian Chen, Zeen Tong, Maria Palmisano, Simon Zhou
Background: Enasidenib (IDHIFA® , AG-221) is a first-in-class, targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia. This was a Phase I/II study evaluating safety, efficacy, and pharmacokinetics/pharmacodynamics (PK/PD) of orally administered enasidenib in subjects with advanced hematologic malignancies with an IDH2 mutation. Methods: Blood samples for PK and PD assessment were collected. A semi-mechanistic nonlinear mixed effect PK/PD model was successfully developed to characterize enasidenib plasma PK and to assess enasidenib-induced CYP3A activity...
2019: Clinical Pharmacology: Advances and Applications
Maxim Clauwaert, Patrick Druwé, Pieter Depuydt
BACKGROUND: Rothia mucilaginosa is a Gram-positive bacterium occurring as a commensal in the oral cavity and upper respiratory tract. Although rarely pathogenic in an immunocompetent host, it can cause severe opportunistic infections in immunocompromised individuals. CASE PRESENTATION: A 67-year-old white woman had a routine blood analysis before undergoing knee surgery. The results showed leukopenia for which bone marrow examination was performed, showing an underlying acute myeloid leukemia...
March 12, 2019: Journal of Medical Case Reports
Jesse A Sharp, Alexander P Browning, Tarunendu Mapder, Kevin Burrage, Matthew J Simpson
Acute myeloid leukaemia (AML) is a blood cancer affecting haematopoietic stem cells. AML is routinely treated with chemotherapy, and so it is of great interest to develop optimal chemotherapy treatment strategies. In this work, we incorporate an immune response into a stem cell model of AML, since we find that previous models lacking an immune response are inappropriate for deriving optimal control strategies. Using optimal control theory, we produce continuous controls and bang-bang controls, corresponding to a range of objectives and parameter choices...
March 7, 2019: Journal of Theoretical Biology
Maura Gasparetto, Shanshan Pei, Mohammad Minhajuddin, Brett Stevens, Clayton A Smith, Paul Seligman
Iron metabolism is altered in a variety of cancers; however, little is known about the role of iron metabolism in the biology and response to therapy of acute myeloid leukemia (AML). Here we show that SLC40A1, the gene encoding the iron exporter ferroportin (FPN), is variably expressed among primary AMLs and that low levels are associated with good prognosis and improved outcomes. In particular, core binding factor (CBF) AMLs, which are associated with good outcomes with chemotherapy, consistently have low level of SLC40A1 expression...
February 28, 2019: Leukemia Research
Wenjing Ma, Yuchen Xiang, Rui Yang, Te Zhang, Jiaxin Xu, Yezi Wu, Xuewen Liu, Ke Xiang, Huzi Zhao, Ying Liu, Yuan Si
Acute myeloid leukemia (AML) is the most common subtype of hematological malignancy in humans, and its incidence increases with age. The treatment of AML still faces challenges. Therefore, there is an urgent need to develop more effective targeted therapies. The receptor tyrosine kinase C-KIT confers critical proliferative signals to AML. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an endogenous inhibitor of protein phosphatase 2A (PP2A), which promotes the growth and transformation of various solid tumors...
February 19, 2019: Journal of Pharmacological Sciences
Li-Wen Huang, Sandy W Wong, Charalambos Andreadis, Rebecca L Olin
PURPOSE OF REVIEW: Hematologic malignancies are common and difficult to treat in older adults. In this review, we focus on recent updates in diseases with several novel agents relevant to older adults-acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM). RECENT FINDINGS: In AML, CPX-351 offers a new induction chemotherapy for secondary AML that prolongs survival, and venetoclax and IDH inhibitors are efficacious and well tolerated...
March 8, 2019: Current Oncology Reports
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