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secondary acute myeloid leukemia

Dilana Staudt, Heather C Murray, Tabitha McLachlan, Frank Alvaro, Anoop K Enjeti, Nicole M Verrills, Matthew D Dun
The identification of recurrent driver mutations in genes encoding tyrosine kinases has resulted in the development of molecularly-targeted treatment strategies designed to improve outcomes for patients diagnosed with acute myeloid leukemia (AML). The receptor tyrosine kinase FLT3 is the most commonly mutated gene in AML, with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) or missense mutations in the tyrosine kinase domain (FLT3-TKD) present in 30⁻35% of AML patients at diagnosis...
October 16, 2018: International Journal of Molecular Sciences
Dennis Liang Fei, Tao Zhen, Benjamin Durham, John Ferrarone, Tuo Zhang, Lisa Garrett, Akihide Yoshimi, Omar Abdel-Wahab, Robert K Bradley, Paul Liu, Harold Varmus
Mutations affecting the spliceosomal protein U2AF1 are commonly found in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML). We have generated mice that carry Cre-dependent knock-in alleles of U2af1 (S34F), the murine version of the most common mutant allele of U2AF1 encountered in human cancers. Cre-mediated recombination in murine hematopoietic lineages caused changes in RNA splicing, as well as multilineage cytopenia, macrocytic anemia, decreased hematopoietic stem and progenitor cells, low-grade dysplasias, and impaired transplantability, but without lifespan shortening or leukemia development...
October 15, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yasuyoshi Morita
Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by cytopenia and leukemic transformation. Allogeneic hematopoietic stem cell transplantation is the only potential curative therapy for MDS; however, the first treatment option for transfusion-independent patients with low-risk MDS remains limited. Recently, lenalidomide has become available for patients with low-risk MDS and symptomatic anemia with del (5q) (5q-syndrome), darbepoetin (DA) for those with anemia without del (5q), and azacitidine for those with DA-resistant anemia or anemia with thrombocytopenia...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Tetsu Hirakawa, Masaya Taniwaki, Ryouta Imanaka, Noboru Hattori
No abstract text is available yet for this article.
October 8, 2018: QJM: Monthly Journal of the Association of Physicians
Kazuaki Yokoyama, Eigo Shimizu, Nozomi Yokoyama, Sousuke Nakamura, Rika Kasajima, Miho Ogawa, Tomomi Takei, Mika Ito, Asako Kobayashi, Rui Yamaguchi, Seiya Imoto, Satoru Miyano, Arinobu Tojo
Acute myeloid leukemia (AML) is a clonal myeloid neoplasm that typically arises de novo; however, some cases evolve from a preleukemic state, such as myelodysplastic syndrome (MDS). Such secondary AMLs and those with typical MDS-related clinical features are known as AMLs with myelodysplasia-related changes (AML-MRC). Because patients with AML-MRC have poor prognosis, more accurate diagnostic approaches are required. In this study, we performed targeted sequencing of 54 genes in 3 cell populations (granulocyte, blast, and T-cell fractions) using samples from 13 patients with MDS, 16 patients with clinically diagnosed AML-MRC, 4 patients with suspected AML-MRC but clinically diagnosed as AML not otherwise specified (AML-NOS), and 11 patients with de novo AML...
October 9, 2018: Blood Advances
Rahul Shenolikar, Emily Durden, Nicole Meyer, Gregory Lenhart, Kathleen Moore
OBJECTIVE: Real-world data on patients with cancer developing secondary malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are lacking. This study assessed the incidence and impact of select DNA-damaging therapy exposure on risk of secondary MDS and AML in patients with ovarian cancer (OC) or breast cancer (BC). METHODS: Adults with a first observed OC or BC diagnosis (index date) between 1/1/2000 and 6/30/2014 were identified from MarketScan® Commercial and Medicare databases...
September 26, 2018: Gynecologic Oncology
Arnaud Pigneux, Marie C Béné, Louis-Rachid Salmi, Pierre-Yves Dumas, Jacques Delaunay, Caroline Bonmati, Romain Guièze, Isabelle Luquet, Pascale Cornillet-Lefebvre, Eric Delabesse, Jean-Christophe Ianotto, Mario Ojeda-Uribe, Mathilde Hunault, Anne Banos, Luc Matthieu Fornecker, Marc Bernard, Eric Jourdan, Norbert Vey, Hacene Zerazhi, Yosr Hishri, Ariane Mineur, Julien Asselineau, Roselyne Delepine, Jean-Yves Cahn, Norbert Ifrah, Christian Récher
PURPOSE: Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin...
September 27, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Shao-Xue Ding, Tong Chen, Ting Wang, Chun-Yan Liu, Wen-Li Lu, Rong Fu
OBJECTIVES: This meta-analysis aimed to evaluate the risk of clonal evolution of granulocyte colony-stimulating factor (G-CSF) in acquired aplastic anemia (AA), and whether the use of G-CSF increases the occurrence of secondary malignant neoplasms, mainly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) or paroxysmal nocturnal hemoglobinuria (PNH). METHODS: Data were gathered from randomized controlled trials (RCTs) to evaluate the effect of G-CSF versus no G-CSF at the risk of developing the clonal complications of acquired AA...
September 25, 2018: Acta Haematologica
Diego Avellaneda Matteo, Grace A Wells, Lucas A Luna, Adam J Grunseth, Olga Zagnitko, David A Scott, An Hoang, Amit Luthra, Manal A Swairjo, Jamie M Schiffer, Christal D Sohl
Mutations in isocitrate dehydrogenase 1 (IDH1) drive most low-grade gliomas and secondary glioblastomas and many chondrosarcomas and acute myeloid leukemia cases. Most tumor-relevant IDH1 mutations are deficient in the normal oxidization of isocitrate to α-ketoglutarate (αKG) but gain the neomorphic activity of reducing αKG to D -2-hydroxyglutarate (D2HG), which drives tumorigenesis. We found previously that IDH1 mutants exhibit one of two reactivities: deficient αKG and moderate D2HG production (including commonly observed R132H and R132C) or moderate αKG and high D2HG production (R132Q)...
September 24, 2018: Biochemical Journal
Andrew Kuykendall, Nicolas Duployez, Nicolas Boissel, Jeffrey E Lancet, John S Welch
Acute myeloid leukemia (AML) was initially subdivided according to morphology (the French-American-British system), which proved helpful in pathologic categorization. Subsequently, clinical and genomic factors were found to correlate with response to chemotherapy and with overall survival. These included a history of antecedent hematologic disease, a history of chemotherapy or radiation therapy, the presence of various recurrent cytogenetic abnormalities, and, more recently, the presence of specific point mutations...
May 23, 2018: American Society of Clinical Oncology Educational Book
Shiro Tara, Yusuke Isshiki, Yaeko Nakajima-Takagi, Motohiko Oshima, Kazumasa Aoyama, Tomoyuki Tanaka, Daisuke Shinoda, Shuhei Koide, Atsunori Saraya, Satoru Miyagi, Ichiro Manabe, Hirotaka Matsui, Haruhiko Koseki, Vivian J Bardwell, Atsushi Iwama
BCOR , encoding BCL-6 co-repressor (BCOR), is X-linked and targeted by somatic mutations in various hematological malignancies including myelodysplastic syndrome (MDS). We previously reported that mice lacking Bcor exon 4 ( BcorΔE4/y ) in the hematopoietic compartment developed NOTCH-dependent acute T-cell lymphoblastic leukemia (T-ALL). Here, we analyzed mice lacking Bcor exons 9 and 10 ( BcorΔE9-10/y ), which express a carboxyl-terminal truncated BCOR that fails to interact with core effector components of polycomb repressive complex (PRC) 1...
September 18, 2018: Blood
Abdulsamad Wafa, Suher ALmedania, Abdulmunim Aljapawe, Thomas Liehr, Soulaiman E Soulaiman, Raja Mouna, Moneeb A K Othman, Walid ALachkar
Background: Chromosomal abnormalities are diagnostic and prognostic key factors in acute myeloid leukemia (AML) patients, as they play a central role for risk stratification algorithms. High hyperdiploidy (HH), a rare cytogenetic abnormality seen commonly in elder male AML patients, is normally categorized under AML with complex karyotype (CK). Accordingly, patients with HH generally are associated with low remission rates and a short overall survival. Case presentation: Here we report a case of 21-year-old female, diagnosed with a de novo AML-M1 according to WHO classification and a CK at diagnosis...
2018: BMC Hematology
Minghua Cao, Ruben D Carrasco, Adrian M Dubuc, Paola Dal Cin, Jonathan A Fletcher, Sheng Xiao
No abstract text is available yet for this article.
August 30, 2018: Leukemia & Lymphoma
Anna L Godfrey, Peter J Campbell, Cathy MacLean, Georgina Buck, Julia Cook, Julie Temple, Bridget S Wilkins, Keith Wheatley, Jyoti Nangalia, Jacob Grinfeld, Mary Frances McMullin, Cecily Forsyth, Jean-Jacques Kiladjian, Anthony R Green, Claire N Harrison
Purpose Cytoreductive therapy is beneficial in patients with essential thrombocythemia (ET) at high risk of thrombosis. However, its value in those lacking high-risk features remains unknown. This open-label, randomized trial compared hydroxycarbamide plus aspirin with aspirin alone in patients with ET age 40 to 59 years and without high-risk factors or extreme thrombocytosis. Patients and Methods Patients were age 40 to 59 years and lacked a history of ischemia, thrombosis, embolism, hemorrhage, extreme thrombocytosis (platelet count ≥ 1,500 × 109 /L), hypertension, or diabetes requiring therapy...
August 28, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Hui-Jen Tsai, Weir-Torn Jiaang, Neng-Yao Shih, Jonathan A Fletcher, Ming-Jon Lin, Ming-Yu Yang, Chiung-Tong Chen, Tsu-An John Hsu, Chun-Chieh Wu, Hui-You Lin, Li-Tzong Chen
Gastrointestinal stromal tumor (GIST) is a prototype of KIT-driven cancer. KIT gene mutations are found in approximately 80% of GIST, and most of these mutations occur in exon 9 and exon 11. Imatinib has been successfully used as a first-line treatment for advanced GIST, with a significant improvement in progression-free survival (PFS) and overall survival. However, disease progression may develop due to primary or secondary resistance to imatinib. Sunitinib and regorafenib have been approved as second- and third-line treatments for advanced GIST patients, with median PFS values of 6...
August 24, 2018: Cancer Science
Dandan Li, Tara L Lin, Brea Lipe, Richard A Hopkins, Heather Shinogle, Omar S Aljitawi
Acute myeloid leukemia (AML) relapse results from the survival of chemotherapy-resistant and quiescent leukemia stem cells (LSC). These LSCs reside in the bone marrow microenvironment, comprised of other cells and extracellular matrix (ECM), which facilitates LSC quiescence through expression of cell adhesion molecules. We used decellularized Wharton's jelly matrix (DWJM), the gelatinous material in the umbilical cord, as a scaffolding material to culture leukemia cells, because it contains many components of the bone marrow extracellular matrix, including collagen, fibronectin, lumican, and hyaluronic acid (HA)...
September 2018: Leukemia Research
Shenglei Ge, Ganghua Zhu, Yan Yi
Extramedullary plasmacytoma (EMP) of the larynx is an extremely rare plasma cell neoplasm outside of the bone marrow, which has not been previously well characterized. A case of laryngeal EMP who developed acute myeloid leukemia (AML) following treatment is described in the present study, as well as an extensive review of the relevant literature. An electronic literature search was performed in PubMed and all pertinent case reports and series in the English language from 1948-October 2017 were identified. A total of 99 cases including the present case were available for review...
September 2018: Oncology Letters
George E Georges, Kris Doney, Rainer Storb
Treatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive therapy (IST) for the treatment of aplastic anemia and then summarize the recommendations for first-line treatment. Based on recent data, we argue that guidelines for the initial treatment of patients with newly diagnosed severe aplastic anemia require revision. At the time of diagnosis, before beginning treatment, HLA typing should be done to identify a marrow donor among family members or in the unrelated donor registries, and a marrow transplant should be considered first-line therapy...
August 14, 2018: Blood Advances
Sung-Soo Park, Young-Woo Jeon, Gi June Min, Silvia Park, Seung-Ah Yahng, Jae-Ho Yoon, Seung-Hwan Shin, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Seok Lee, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee, Yoo-Jin Kim
Graft-versus-host disease-free, relapse-free survival (GRFS) is a composite endpoint that measures survival free of relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Consecutive adult patients (N = 324) who received HSCT with fludarabine and busulfan-based conditioning for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia evolved from MDS were retrospectively analyzed. One-year and 3-year GRFS rates were 47.8% and 34.5%, respectively. Three fixed factors (circulating blast > 3%, high cytogenetic risk, and high comorbidity index) and 2 factors (which are) modifiable by clinicians (myeloablative conditioning [MAC] and low-dose [<7...
August 10, 2018: Biology of Blood and Marrow Transplantation
G H Lyman, L Yau, R Nakov, A Krendyukov
Background: The use of supportive granulocyte colony-stimulating factor (G-CSF) to reduce the risk of neutropenic complications in high-risk cancer patients is consistently recommended by several clinical practice guidelines. However, in a previous meta-analysis, G-CSF prophylaxis was associated with an increased risk of secondary malignancies while reducing long-term mortality. We present here an updated systematic review and meta-analysis. Materials and methods: A systematic literature search was carried out to identify randomized controlled trials of cancer patients receiving conventional-dose chemotherapy, assigned to primary G-CSF support or a control group without initial G-CSF, with at least 2 years of follow-up...
September 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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