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Myeloblastic leukemia

Harrison T Supnick, Rodica P Bunaciu, Andrew Yen
Differentiation therapy is used in cancer treatment. Epidemiologic studies showed that higher vitamin D levels are associated with reduced cancer risks. However, the therapeutic doses needed for differentiation are accompanied by hypercalcemia and intolerable pathological sequelae. In the present work we evaluated if RRD-251, a small-molecule, can enhance vitamin D3-induced differentiation of leukemic cells, in the hope of decreasing the needed vitamin D3-dose. We demonstrate that RRD-251 enhances vitamin D3-induced differentiation of leukemic cells, the enrichment of the c-Raf kinase in the nucleus, the binding of nuclear c-Raf to GSK-3, increased phosphorylation of GSK-3 ser 21/9 inhibitory sites, and the binding of GSK-3 to VDR, where GSK-3 inhibition is known to enhance transcriptional activation by VDR...
February 9, 2018: Oncotarget
Weijie Li, Linda D Cooley, Keith August
Juvenile myelomonocytic leukemia (JMML) is a rare aggressive childhood leukemia characterized by an excess proliferation of cells of granulocytic and monocytic lineages. The WHO classifies JMML with the myelodysplastic/myeloproliferative neoplasms. Myelodysplasia in JMML is usually minimal to mild. Auer rods have never been reported in JMML. We present a 2-year-old boy with splenomegaly, leukocytosis, thrombocytopenia, anemia, and excess myeloblasts with easily seen Auer rods, and marked dysgranulopoiesis and dyserythropoiesis...
December 5, 2017: Pathology, Research and Practice
Can Boga, Mahmut Yeral, Ciğdem Gereklioglu, Suheyl Asma, Erkan Maytalman, Pelin Aytan, Ilknur Kozanoglu, Cagla Sariturk, Hakan Ozdogu
OBJECTIVE/BACKGROUND: Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known...
February 20, 2018: Hematology/oncology and Stem Cell Therapy
Kosuke Akiyama, Shohei Yamamoto, Yumiko Sugishita, Ryota Kaneko, Naoko Okamoto, Masaya Koganesawa, Sachio Fujita, Ryosuke Matsuno, Daisuke Toyama, Keiichi Isoyama
A 9-year-old girl was referred to our hospital because of facial palsy. Both physical and blood examination revealed hepatosplenomegaly and leukocytosis, respectively. A bone marrow examination demonstrated marked hypercellularity involving myeloblasts and lymphoblasts. Based on these results, we suspected mixed phenotype acute leukemia. However, her leukemic blasts expressed B-cell antigens, and a chromosomal analysis of her bone marrow cells revealed the following karyotype: 46, XX, t (9;22) (q34;q11.2). All her neutrophils were positive for the breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion protein...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Jinah Park, Junil Kim, Bora Park, Kyung-Min Yang, Eun Jin Sun, Cristina E Tognon, Poul H Sorensen, Seong-Jin Kim
Chromosomal rearrangements that facilitate tumor formation and progression through activation of oncogenic tyrosine kinases are frequently observed in cancer. The ETV6-NTRK3 (EN) fusion has been implicated in various cancers, including infantile fibrosarcoma, secretory breast carcinoma, and acute myeloblastic leukemia, and has exhibited in vivo and in vitro transforming ability. In the present study, we analyzed transcriptome alterations using DNA microarray and RNA-Seq in EN-transduced NIH3T3 fibroblasts to identify the mechanisms that are involved in EN-mediated tumorigenesis...
February 2, 2018: Oncogene
Stephanie Grainger, David Traver, Karl Willert
Leukemia and lymphoma are a wide encompassing term for a diverse set of blood malignancies that affect people of all ages and result in approximately 23,000 deaths in the United States per year (Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.). Hematopoietic stem cells (HSCs) are tissue-specific stem cells at the apex of the hierarchy that gives rise to all of the terminally differentiated blood cells, through progressively restricted progenitor populations, a process that is known to be Wnt-responsive...
January 2018: Progress in Molecular Biology and Translational Science
Amir T Fathi, Courtney D DiNardo, Irina Kline, Laurie Kenvin, Ira Gupta, Eyal C Attar, Eytan M Stein, Stephane de Botton
Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity...
January 18, 2018: JAMA Oncology
Vincent T Ho, Haesook T Kim, Natalie Bavli, Martin Mihm, Olga Pozdnyakova, Matthias Piesche, Heather Daley, Carol Reynolds, Nicholas C Souders, Corey Cutler, John Koreth, Edwin P Alyea, Joseph H Antin, Jerome Ritz, Glenn Dranoff, Robert J Soiffer
We report a clinical trial testing vaccination of autologous myeloblasts admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells after allogeneic hematopoietic stem cell transplantation (HSCT). Patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with ≥5% marrow blasts underwent myeloblast collection before HSCT. At approximately day +30, 6 vaccines composed of irradiated autologous myeloblasts mixed with GM-K562 were administered. Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis was not tapered until vaccine completion (∼day 100)...
November 14, 2017: Blood Advances
Sogyong L Auh, Ingrid Polcari, Vesna Petronic-Rosic, Aisha Sethi
A 79-year-old man with a recent diagnosis of acute myeloblastic leukemia received induction chemotherapy with daunorubicin and cytarabine, plus moxifloxacin and fluconazole prophylaxis. Approximately 2 weeks later, an asymptomatic eruption appeared on his trunk. He then developed a neutropenic fever and was started on aztreonam, vancomycin, voriconazole, and amikacin and was transferred to our facility from an outside hospital. Micafungin was subsequently added, and the patient defervesced within a few days...
2017: Skinmed
Jessica Lee, Soraya Azzawi, Michael J Peluso, Aaron Richterman, Haiyan Ramirez Batlle, Maria A Yialamas
We report the case of a 51-year-old woman presenting with a targetoid rash and pancytopenia after a tick bite. Initial evaluation was notable for severe neutropenia on the complete blood cell count differential, a positive Lyme IgM antibody, and a peripheral blood smear demonstrating atypical lymphocytes. While her pancytopenia was initially attributed to tick-borne illness, peripheral flow cytometry showed 7% myeloblasts, and a bone marrow biopsy confirmed 60% blasts. The patient was ultimately diagnosed with acute myelogenous leukemia, in addition to early, localized Lyme disease...
December 22, 2017: Journal of General Internal Medicine
Francis Lacombe, Lydia Campos, Kaoutar Allou, Christine Arnoulet, Adrienne Delabarthe, Florent Dumezy, Jean Feuillard, Franck Geneviève, Estelle Guérin, Julien Guy, Hélène Jouault, Pascale Lepelley, Marc Maynadié, Françoise Solly, Orianne Wagner Ballon, Claude Preudhomme, André Baruchel, Hervé Dombret, Norbert Ifrah, Marie C Béné
The assessment of minimal residual disease (MRD) in acute myeloblastic leukemia is of growing interest as a prognostic marker of patients' outcome. Multiparameter flow cytometry (MFC), tracking leukemia-associated immunophenotypic patterns, has been shown in several studies to be a useful tool to investigate MRD. Here, we report a multicenter prospective study which allowed to define a harmonized analysis strategy, as well as the efficacy of MFC MRD to predict outcome. This study included 276 patients, in 10 different MFC centers, of whom 268 had at least 1 MRD check point...
December 7, 2017: Hematological Oncology
Marzena Wątek, Bonita Durnaś, Tomasz Wollny, Marcin Pasiarski, Stanisław Góźdź, Michał Marzec, Anna Chabowska, Przemysław Wolak, Małgorzata Żendzian-Piotrowska, Robert Bucki
BACKGROUND: Impaired apoptotic pathways in leukemic cells enable them to grow in an uncontrolled way. Moreover, aberrations in the apoptotic pathways are the main factor of leukemic cells drug resistance. METHODS: To assess the presence of potential abnormalities that might promote dysfunction of leukemic cells growth, HPLC system was used to determine sphingosine (SFO), sphinganine (SFA), sphingosine-1-phosphate (S1P) and ceramide (CER) concentration in the blood collected from patients diagnose with acute myeloblastic leukemia (AML; n = 49) and compare to values of control (healthily) group (n = 51)...
December 8, 2017: Lipids in Health and Disease
Vu H Duong, Eric Padron, Najla H Al Ali, Jeffrey E Lancet, Jeff Hall, Brian Kwok, Ling Zhang, Pearlie K Epling-Burnette, Alan F List, Rami S Komrokji
The prognostic value of peripheral blasts (PB) is not well-studied in patients with myelodysplastic syndromes (MDS). We evaluated the impact of PB on overall survival (OS) and transformation to acute myeloid leukemia (AML) in a large cohort. The MDS database at the Moffitt Cancer Center was retrospectively reviewed to identify patients with ≥ 1% PB (PB-MDS) and those without PB (BM-MDS). We also assessed the correlation between PB and gene mutations. One thousand seven hundred fifty-eight patients were identified, among whom 13% had PB near the time of diagnosis...
February 2018: Annals of Hematology
Stefano Rossetti, Michael J Anauo, Nicoletta Sacchi
RUNX1, a master transcription factor of hematopoiesis, was shown to orchestrate both cell proliferation and differentiation during granulopoiesis by regulating microRNAs (miRs). In this study, taking advantage of the miR-ON reporter system, we monitored first, how the granulocyte colony stimulation factor (GCSF) temporally modulates the concomitant level variation of miR-221 and one of its prototypic targets, the stem cell factor receptor KIT, in single 32DmiR-ON-221 myeloblasts expressing wild type RUNX1. Second, with the same reporter system we assessed how these temporal dynamics are affected by the t(8;21)(q22;q22) acute myelogenous leukemia mutant RUNX1-MTG8 (RM8) in single 32D-RM8miR-ON-221 myeloblasts...
October 17, 2017: Oncotarget
Yoshitaka Adachi, Yohei Yamaguchi, Ken Sagou, Yusuke Yamaga, Nobuaki Fukushima, Kazutaka Ozeki, Akio Kohno
A 64-year-old man with acute myeloid leukemia underwent umbilical cord blood transplantation (UCBT). After 11 months of complete remission (CR) following UCBT, the bone marrow showed 7.5% myeloblasts. CR was obtained after a single course of azacitidine monotherapy, but the myeloblasts gradually increased in the blood. We made a diagnosis of acute megakaryoblastic leukemia derived from donor cell with a fluorescence in situ hybridization (FISH) analysis of the sex chromosomes and an immunophenotypic analysis...
November 20, 2017: Internal Medicine
Hakan Ozdogan, Bala Gur Dedeoglu, Yasemin Oztemur Islakoglu, Alp Aydos, Sevil Kose, Arzu Atalay, Zeynep Arzu Yegin, Ferit Avcu, Duygu Uckan Cetinkaya, Osman Ilhan
Multipotent mesenchymal stem cells (MSC) are key components of the bone marrow (BM) microenvironment. The contribution of this microenvironment to the pathophysiology of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is not well defined. A recent study in mice demonstrated that DICER1 gene deletion in osteoprogenitor cells from the BM microenvironment suppressed osteogenic differentiation and induced MDS and AML-like haematological findings. The present study evaluated the expression profiles of microRNAs (miRNAs) and DICER1 gene in BM-derived MSC of patients with AML (n=12), MDS (n=10) and healthy controls (HC) (n=8)...
December 2017: Leukemia Research
Malgorzata Opydo-Chanek, Katarzyna Śladowska, Kamil Blicharski, Jaromir Mikeš, Peter Fedoročko, Ulf Niemeyer, Lidia Mazur
BACKGROUND/AIM: The oxazaphosphorines, ifosfamide and cyclophosphamide, represent a class of alkylating agents. The aim of the present in vitro study was to compare antileukemic activity of 4-hydroperoxyifosfamide (4-OOH-IF) and 4-hydroperoxycyclophosphamide (4-OOH-CP). MATERIALS AND METHODS: The experiments were performed on MOLT-4 and ML-1 cells. The research was conducted using flow cytometry fluorescein diacetate/propidium iodide (PI), fluorescein-conjugated annexin V/PI, CaspGLOW Red Active Caspase-8 and -9, CellEvent™ Caspase-3/7 Green assays, and tetramethylrhodamine ethyl ester test...
November 2017: Anticancer Research
Vlad Voin, Shehzad Khalid, Sebastian Shrager, R Shane Tubbs, Robert Greiner, Krishnamoorthy Thamburaj, Elias Rizk
Extramedullary tumors composed of myeloblasts or monoblasts can present in various locations. Patients with a history of acute myeloid leukemia (AML) can present with neuropathic pain and no evidence of relapse of their leukemia. Neuroleukemiosis is a form of extramedullary tumor present in the peripheral nervous systems (PNS) of leukemia patients. We report two AML patients who were in remission and later presented with neurological symptoms due to neuroleukemiosis with negative bone marrow biopsies.
July 31, 2017: Curēus
H Youn, H-K Lee, H-R Sohn, U-H Park, E-J Kim, B Youn, S-J Um
Retinoic acid (RA) has broad clinical applications for the treatment of various cancers, particularly acute promyelocytic leukemia. However, RA-based therapy is limited by relapse in patients associated with RA resistance, the mechanism of which is poorly understood. Here, we suggest a new molecular mechanism of RA resistance by a repressor, named RA resistance factor (RaRF). RaRF suppressed transcriptional activity of the RA receptor (RAR) by directly interacting with and sequestering RAR to the nucleolus in response to RA...
September 25, 2017: Oncogene
Bao Yang, Chenlong Yang, Jingyi Fang, Jun Yang, Yulun Xu
Myeloid sarcoma (MS) is a localized tumor composed of premature precursors of granulocytic cells, which may occur in any organ and most commonly involves the soft tissue and musculoskeletal system. This malignancy may occur in the presence or absence of hematological disorders. Primary MS involving the central nervous system (CNS-MS) is rare, and has only been described in a small number of isolated case reports. The diagnosis of CNS-MS is challenging and strategies for its management are undefined. The present study describes 4 cases of CNS-MS...
September 2017: Oncology Letters
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