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Acute Myelogenic Leukemia

Yan-Bin Pang, Ping Wu, Luo-Ming Hua, Xin DU, Jing Wang
The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid disorders characterized by ineffective hematopoiesis and increased risk of transformation to acute myelogenous leukemia (AML). The treatment of MDS is highly dependent on the reliability of the prognostic evaluation model. Current clinical prognostic scoring systems are comprised of morphology, pivotal clinical trials and cytogenetic findings. However, none of the available prognostic systems incorporates disease-related molecular abnormalities, such as somatic mutations...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Raza Mushtaq, David Nolte, Faryal Shareef, Mihra S Taljanovic
Acute myelogenous leukemia is a hematologic malignancy defined by the presence of myeloid blasts causing bone marrow infiltration. Evaluation and workup of acute myelogenous leukemia is based on comprehensive medical history, physical examination, laboratory evaluation, and bone marrow sampling. Magnetic resonance (MR) imaging is the study of choice in the evaluation of this disease including the initial evaluation, treatment follow-up, and complications. Herein, we report a case of relapse of the acute myelogenic leukemia in an adult patient who presented with diffuse periostitis in his lower extremities diagnosed on MR imaging and confirmed on Technetium bone scan, which also showed periostitis along the bilateral humeri...
October 2018: Radiology Case Reports
Vikas Madan, Lin Han, Norimichi Hattori, Weoi Woon Teoh, Anand Mayakonda, Qiao-Yang Sun, Ling-Wen Ding, Hazimah Binte Mohd Nordin, Su Lin Lim, Pavithra Shyamsunder, Pushkar Dakle, Janani Sundaresan, Ngan B Doan, Masashi Sanada, Aiko Sato-Otsubo, Manja Meggendorfer, Henry Yang, Jonathan W Said, Seishi Ogawa, Torsten Haferlach, Der-Cherng Liang, Lee-Yung Shih, Tsuyoshi Nakamaki, Q Tian Wang, H Phillip Koeffler
Chromosomal translocation t(8;21)(q22;q22) which leads to generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is observed in about 10% of acute myelogenous leukemia (AML). To uncover somatic mutations that cooperate with t(8;21)-driven leukemia, we performed whole and targeted exome sequencing of an Asian cohort at diagnosis and relapse. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in-depth the role of ASXL2 in normal hematopoiesis, we utilized a mouse model of ASXL2 deficiency...
August 9, 2018: Haematologica
Akanksha Bothale, Kalpana Bothale, Sadhana Mahore, Trupti Dongre
Extramedullary hematopoiesis (EMH) is a compensatory mechanism that occurs when the marrow is unable to maintain sufficient red cell mass. EMH generally occurs in the patients with deficient bone marrow hematopoiesis secondary to either peripheral red cell destruction or marrow replacement. Although EMH is known to occur in agnogenic myeloid metaplasia with myelofibrosis, chronic myelogenous leukemia, thalassemia, and infiltrative disorders, such as lymphomas, it is rare in acute leukemias. EMH is most commonly seen in the liver and spleen as a diffuse lesion...
July 2018: Journal of Cytology
Zhifei Xu, Ying Jin, Hao Yan, Zizheng Gao, Bo Xu, Bo Yang, Qiaojun He, Qiang Shi, Peihua Luo
Dasatinib shows remarkable activity against imatinib-refractory chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). However, severe cardiovascular toxicity limits the clinical applications of dasatinib. Since the underlying mechanism of dasatinib-induced cardiotoxicity is still elusive, we aim to clarify this. Recent studies have shown that necroptosis and apoptosis participate in multiple toxicity development. Here, we first report that dasatinib could directly induce cardiomyocytes death, as analyzed by the Sulforhodamine B (SRB) assay...
August 4, 2018: Toxicology Letters
Kateřina Staňo Kozubík, Lenka Radová, Michaela Pešová, Kamila Réblová, Jakub Trizuljak, Karla Plevová, Veronika Fiamoli, Jaromír Gumulec, Helena Urbánková, Tomáš Szotkowski, Jiří Mayer, Šárka Pospíšilová, Michael Doubek
Here we report a C-terminal RUNX1 mutation in a family with platelet disorder and predisposition to myeloid malignancies. We identified the mutation c.866delG:p.Gly289Aspfs*22 (NM_001754) (RUNX1 b-isoform NM_001001890; c.785delG:p.Gly262Aspfs*22) using exome sequencing of samples obtained from eight members of a single family. The mutation found in our pedigree is within exon eight and the transactivation domain of RUNX1. One of the affected individuals developed myelodysplastic syndrome (MDS), which progressed to acute myelogenous leukemia (AML)...
August 6, 2018: International Journal of Hematology
Amanda Balmages, Joseph Dinglasan, Megan Boysen Osborn
Intracranial hemorrhage (ICH) is the second leading cause of mortality among patients diagnosed with acute myelogenous leukemia (AML). The bone marrow failure associated with AML produces dysfunctional platelets, which significantly increases the risk of hemorrhagic complications within this population. In this report we discuss the case of a previously healthy female patient, newly diagnosed with AML, who rapidly developed fatal ICH.
August 2018: Clinical practice and cases in emergency medicine
Daisuke Hidaka, Masahiro Onozawa, Junichi Hashiguchi, Naohiro Miyashita, Kohei Kasahara, Shinichi Fujisawa, Eiko Hayase, Kohei Okada, Souichi Shiratori, Hideki Goto, Junichi Sugita, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Tomoyuki Endo, Satoshi Yamamoto, Yutaka Tsutsumi, Yoshihito Haseyama, Takahiro Nagashima, Akio Mori, Shuichi Ota, Hajime Sakai, Toshimichi Ishihara, Kiyotoshi Imai, Takuto Miyagishima, Yasutaka Kakinoki, Mitsutoshi Kurosawa, Hajime Kobayashi, Hiroshi Iwasaki, Chikara Shimizu, Takeshi Kondo, Takanori Teshima
BACKGROUND: The prognostic effect of Wilms tumor 1 (WT1) expression at the diagnosis of acute myelogenous leukemia (AML) has been controversial. The aim of the present study was to determine the correlations of WT1 expression at the diagnosis of AML with established prognostic alterations. PATIENTS AND METHODS: We analyzed diagnostic bone marrow samples from 252 patients. WT1 expression, single nucleotide polymorphism (SNP) in the WT1 gene (rs16754), and Fms-like tyrosine kinase receptor-3 internal tandem duplication (FLT3-ITD) mutation were analyzed for all patients...
July 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
Shiro Ide, Shin Ohara, Morihiro Inoue, Jian Hua, Masao Hagihara
A 77-year-old male with hyperleukocytosis and thrombocytopenia was diagnosed with Philadelphia chromosome (Ph) -negative B-cell acute lymphoblastic leukemia (ALL) ; he was treated with induction chemotherapy. Despite an initial complete remission, hyperleukocytosis was returned 18 months later. A bone marrow smear revealed a substantial increase in the number of myeloid cells with each stage of differentiation, which was markedly different from the initial presentation, resulting in the diagnosis of Ph-negative myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Niraj Shenoy, Mythri Mudireddy, Rangit Vallapureddy, Nelson Leung, Lance Pagliaro, Thomas Witzig, Fang-Shu Ou, Tamas Ordog, John Cheville, Mrinal Patnaik, R Houston Thompson, Ayalew Tefferi, Kebede Begna
BACKGROUND: Renal cell carcinoma (RCC) and certain myeloid malignancies are both characterized by widespread aberrant DNA hypermethylation. After clinical observations of patients with a personal history of both malignancies, we sought to explore a potential association, and to describe the clinical characteristics of these patients. PATIENTS AND METHODS: Mayo Clinic's 'Advanced Cohort Explorer' database was used to identify patients with a history of both malignancies...
June 28, 2018: Clinical Genitourinary Cancer
Sarah Nikiforow, Tao Wang, Michael Hemmer, Stephen Spellman, Görgün Akpek, Joseph H Antin, Sung Won Choi, Yoshihiro Inamoto, Hanna J Khoury, Margaret MacMillan, David I Marks, Ken Meehan, Hideki Nakasone, Taiga Nishihori, Richard Olsson, Sophie Paczesny, Donna Przepiorka, Vijay Reddy, Ran Reshef, Hélène Schoemans, Ned Waller, Daniel Weisdorf, Baldeep Wirk, Mary Horowitz, Amin Alousi, Daniel Couriel, Joseph Pidala, Mukta Arora, Corey Cutler
Upper gastrointestinal acute graft-versus-host disease is reported in approximately 30% of hematopoietic stem cell transplant recipients developing acute graft-versus-host disease. Currently classified as Grade II in Consensus criteria, upper gastrointestinal acute graft-versus-host disease is often treated with systemic immunosuppression. We reviewed the Center for International Blood and Marrow Transplant Research database to assess prognostic implications of upper gastrointestinal acute graft-versus-host disease in isolation or with other acute graft-versus-host disease manifestations...
August 3, 2018: Haematologica
Akito Nakamura, Tadahiro Nambu, Shunsuke Ebara, Yuka Hasegawa, Kosei Toyoshima, Yasuko Tsuchiya, Daisuke Tomita, Jun Fujimoto, Osamu Kurasawa, Chisato Takahara, Ayumi Ando, Ryuichi Nishigaki, Yoshinori Satomi, Akito Hata, Takahito Hara
General control nonderepressible 2 (GCN2) plays a major role in the cellular response to amino acid limitation. Although maintenance of amino acid homeostasis is critical for tumor growth, the contribution of GCN2 to cancer cell survival and proliferation is poorly understood. In this study, we generated GCN2 inhibitors and demonstrated that inhibition of GCN2 sensitizes cancer cells with low basal-level expression of asparagine synthetase (ASNS) to the antileukemic agent l-asparaginase (ASNase) in vitro and in vivo...
August 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
Zheng Xu, Huirui Wang, Suhua Wei, Zhencheng Wang, Guanghou Ji
Endoplasmic reticulum (ER) stress is induced in chronic myelogenous leukemia (CML) cells. As an important sensor of ER stress, inositol-requiring protein-1α (IRE1α) promotes the survival of acute myeloid leukemia. NLRP1 inflammasome activation promotes metastatic melanoma growth and that IRE1α can increase NLRP1 inflammasome gene expression. This study aimed to investigate the role and molecular mechanism of IRE1α in CML cell growth. We found that overexpression of IRE1α or NLRP1 significantly promoted the proliferation and decreased the apoptosis of CML cells, whereas downregulation of these two genes showed the opposite effects...
July 25, 2018: Molecular Immunology
Esteban Arrieta-Bolaños, Pietro Crivello, Bronwen E Shaw, Kwang Woo Ahn, Hai-Lin Wang, Michael R Verneris, Katharine C Hsu, Joseph Pidala, Stephanie J Lee, Katharina Fleischhauer, Stephen R Spellman
In silico prediction of high-risk donor-recipient HLA mismatches after unrelated donor (UD) hematopoietic cell transplantation (HCT) is an attractive, yet elusive, objective. Nonpermissive T-cell epitope (TCE) group mismatches were defined by alloreactive T-cell cross-reactivity for 52/80 HLA-DPB1 alleles (TCE-X). More recently, a numerical functional distance (FD) scoring system for in silico prediction of TCE groups based on the median impact of exon 2-encoded amino acid polymorphism on T-cell alloreactivity was developed for all DPB1 alleles (TCE-FD), including the 28/80 common alleles not assigned by TCE-X...
July 24, 2018: Blood Advances
Sameer K Avasarala, Muhammad R Qureshi, Madeline Waldron, Sudipto Mukherjee, Anita J Reddy
Background Acute respiratory failure is a leading cause of intensive care unit admission in patients with hematological malignancies; it carries a mortality rate exceeding 50%. Venovenous extracorporeal membrane oxygenation use in patients with acute hematologic malignancies concurrently receiving induction chemotherapy is not well studied. Case presentation A 44-year-old male developed acute respiratory distress syndrome in the setting of newly diagnosed acute myelogenous leukemia. He underwent successful induction chemotherapy while on venovenous extracorporeal membrane oxygenation...
July 24, 2018: Journal of Oncology Pharmacy Practice
Alexandria A Oviatt, Jissy A Kuriappan, Elirosa Minniti, Kendra R Vann, Princess Onuorah, Anna Minarini, Marco De Vivo, Neil Osheroff
Etoposide is an anticancer drug that acts by inducing topoisomerase II-mediated DNA cleavage. Despite its wide use, etoposide is associated with some very serious side-effects including the development of treatment-related acute myelogenous leukemias. Etoposide targets both human topoisomerase IIα and IIβ. However, the contributions of the two enzyme isoforms to the therapeutic vs. leukemogenic properties of the drug are unclear. In order to develop an etoposide-based drug with specificity for cancer cells that express an active polyamine transport system, the sugar moiety of the drug has been replaced with a polyamine tail...
July 5, 2018: Bioorganic & Medicinal Chemistry Letters
Jonas A Adalsteinsson, Michael Pan, Shivani Kaushik, Jonathan Ungar
Foscarnet is an important antiviral medication used mainly in the treatment of complicated Herpes-simplex virus and cytomegalovirus (CMV) infections. Reported first in the 1990's, genital ulcers are a potential side effect in about 10% of cases. We report the case of a 29 year old man with acute myelogenous leukemia who was on ganciclovir for CMV prophylaxis. Three weeks after being switched to foscarnet because of neutropenia, he developed two, painful symmetric ulcers on the inferior aspect of glans penis...
April 23, 2018: Dermatology Reports
Stefano Sainas, Agnese C Pippione, Elisa Lupino, Marta Giorgis, Paola Circosta, Valentina Gaidano, Parveen Goyal, Davide Bonanni, Barbara Rolando, Alessandro Cignetti, Alex Ducime, Mikael Andersson, Michael Järvå, Rosmarie Friemann, Marco Piccinini, Cristina Ramondetti, Barbara Buccinnà, Salam Al-Karadaghi, Donatella Boschi, Giuseppe Saglio, Marco L Lolli
Human dihydroorotate dehydrogenase ( hDHODH) catalyzes the rate-limiting step in de novo pyrimidine biosynthesis, the conversion of dihydroorotate to orotate. hDHODH has recently been found to be associated with acute myelogenous leukemia, a disease for which the standard of intensive care has not changed over decades. This work presents a novel class of hDHODH inhibitors, which are based on an unusual carboxylic group bioisostere 2-hydroxypyrazolo[1,5- a]pyridine, that has been designed starting from brequinar, one of the most potent hDHODH inhibitors...
July 9, 2018: Journal of Medicinal Chemistry
Yazid Belkacemi, Myriam Labopin, Sebastian Giebel, Norbert Claude Gorin, Gokoulakrichenane Loganadane, Leszek Miszczyk, Mauricette Michallet, Gerard Socié, Nicolaas Pm Schaap, Jan J Cornelissen, Ibrahim Yakoub-Agha, Emmanuelle Polge, Mohamad Mohty, Arnon Nagler
PURPOSE: Total-body irradiation (TBI) is a major constituent of myeloablative conditioning regimens. The standard technique consists of 12Gy in 6 fractions over 3 days. The SARASIN study aimed to compare standard-fractionation to one-daily fractionation prior to transplant in leukemia. MATERIAL AND METHODS: We retrospectively compared TBI regimens delivered in 2993 patients from the EBMT database, transplanted between 2000 and 2014 for acute lymphoblastic (ALL, n=1729) or acute myelogenous (AML, n=1264) leukemia...
June 18, 2018: International Journal of Radiation Oncology, Biology, Physics
Yusuke Noguchi, Daisuke Tomizawa, Haruka Hiroki, Satoshi Miyamoto, Mari Tezuka, Reiji Miyawaki, Mari Tanaka-Kubota, Tubasa Okano, Chika Kobayashi, Noriko Mitsuiki, Yuki Aoki, Kohsuke Imai, Michiko Kajiwara, Hirokazu Kanegane, Tomohiro Morio, Masatoshi Takagi
Myeloid/natural killer cell precursor acute leukemia (MNKPL) is a rare leukemia subtype characterized by a high incidence of extramedullary infiltration. No appropriate treatment strategy has so far been developed. Acute myelogenous leukemia-type chemotherapy combined with L-Asparaginase is an effective treatment for MNKPL. Hematopoietic cell transplantation is a second option in refractory cases.
June 2018: Clinical Case Reports
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