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Acute leukemias

Maggie Brett, Angeline H M Lai, Teck-Wah Ting, Ah-Moy Tan, Roger Foo, Saumya Jamuar, Ene-Choo Tan
No abstract text is available yet for this article.
October 19, 2016: American Journal of Medical Genetics. Part A
Jolanta Skalska-Sadowska, Małgorzata Dawidowska, Bronisława Szarzyńska-Zawadzka, Małgorzata Jarmuż-Szymczak, Joanna Czerwińska-Rybak, Ludomiła Machowska, Katarzyna Derwich
We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1(wt) , FBXW7(wt) , STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations...
October 19, 2016: Pediatric Blood & Cancer
Sergio Pina-Oviedo, Carlos A Torres-Cabala, Roberto N Miranda, Michael T Tetzlaff, Selina Singh, Ronald P Rapini, Victor G Prieto, Phyu P Aung
Leukemia cutis develops in <4% of all acute leukemias. Concurrent acute myeloid leukemia (AML) and Langerhans cell histiocytosis (LCH) is rare, with most cases involving lymph nodes or spleen, and no cutaneous involvement. We report the case of a 59-year-old man who presented with fever, malaise, and fatigue. The CBC showed leukocytosis (30.4 × 10/L, 9% blasts), anemia, and thrombocytopenia. Bone marrow biopsy was diagnosed with AML, not otherwise specified, with mutations of FLT3 and IDH2 (R140Q). The patient developed skin rash on the right flank with the clinical differential diagnosis of herpes simplex virus or varicella-zoster virus infection/reactivation versus leukemia cutis...
October 18, 2016: American Journal of Dermatopathology
Giang Huong Nguyen, James Y Wang, Kenneth B Hymes, Cynthia M Magro
Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities...
October 12, 2016: American Journal of Dermatopathology
Xavier Thomas, Caroline Le Jeune
Advances in acute lymphocytic leukemia (ALL) therapy has led to long-term survival rates in children. However, only 30%-40% of adults achieve long-term disease-free survival. After relapse, the outcome of salvage chemotherapy is very disappointing with less than 10% of long survival. Novel agents are therefore desperately required to improve response rates and survival, but also the quality of life of patients. Areas covered. The following review is a comprehensive summary of various novel options reported over the past few years in the therapeutic area of adult ALL...
October 19, 2016: Expert Opinion on Pharmacotherapy
Michael Medinger, Claudia Lengerke, Jakob Passweg
Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades...
2016: Leukemia Research Reports
Steven Wang, Jie Yan, Guangde Zhou, Rebecca Heintzelman, J Steve Hou
Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies characterized by unchecked proliferation of differentiated myeloid cells. The most common BCR-ABL1-negative MPNs are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The discovery of JAK2 V617F mutation has improved our understanding of the molecular basis of MPN. The high frequency of JAK2 mutation in MPN makes JAK2 mutation testing an essential diagnostic tool and potential therapeutic target for MPN. Here, we present a rare case of a 34-year-old patient who was initially diagnosed with acute myeloid leukemia (AML) with mutated NPM1...
2016: Case Reports in Hematology
Junqing Xu, Baohua Huang, Xiaoqian Liu, Yuanfeng Zhang, Yinghui Liu, Liming Chen, Yanyan Luan, Nannan Li, Xiaoxia Chu
This study aimed to investigate the clinical characteristics and prognostic significance of monosomal karyotype (MK) in patients with acute myeloid leukemia (AML). We retrospectively analyzed the clinical data for 498 patients with AML, of whom 233 (46.8%) had an abnormal karyotype, including 42 with MK (8.4%) and 70 with a complex karyotype (CK) (14.1%). Patients with MK were older (median age 62.5 vs. 52 years, P=0.003), and had lowermedian hemoglobin levels (62.5 vs. 77 g/L, P=0.009) and lower white blood cell counts (7...
October 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Ivana Milosevic
A 76-years old man presented with leucocytosis (86x109/l), fever, pneumonia and significant weight loss. He had a history of chronic lymphocytic leukemia diagnosed five years earlier and he responded with partial remission to the treatment with continuous low doses of chlorambucil. Analysis of blood smear, bone marrow aspiration and bone marrow biopsy revealed predomination of small lymphocytes, but 22% of cells were blasts negative to cytochemical stainings (Figure 1). Flow cytometric analysis showed two distinct populations: 65% of cells was small to moderate in size, CD19+, CD45+, CD5+, CD20+/-, but 30% of cells were large, CD34+, CD13+, HLA DR+, CD65+, CD45+, MPO weakly positive and CD33, CD14, CD15, CD16 negative...
October 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Anna Palau, Mar Mallo, Laura Palomo, Ines Rodríguez-Hernández, Jeannine Diesch, Diana Campos, Isabel Granada, Jordi Juncà, Hans G Drexler, Francesc Solé, Marcus Buschbeck
Leukemia cell lines have been widely used in the hematology field to unravel mechanistic insights and to test new therapeutic strategies. Myelodysplastic syndromes (MDS) comprise a heterogeneous group of diseases that are characterized by ineffective hematopoiesis and frequent progress to acute myeloid leukemia (AML). A few cell lines have been established from MDS patients after progression to AML but their characterization is incomplete. Here we provide a detailed description of the immunophenotypic profile of the MDS-derived cell lines SKK-1, SKM-1, F-36P; and MOLM-13...
October 17, 2016: Genes, Chromosomes & Cancer
Yu Mi Seo, Seok Hwang-Bo, Seong Koo Kim, Seung Beom Han, Nack-Gyun Chung, Jin Han Kang
BACKGROUND: Although adenovirus (ADV) infection usually causes self-limiting respiratory disorders in immune competent children; severe and systemic ADV infection in children undergoing chemotherapy for leukemia has been continuously reported. Nevertheless, there has been no consensus on risk factors and treatment strategies for severe ADV infection in children undergoing chemotherapy. CASE SUMMARY: We report a case of a 15-year-old boy with a fatal systemic ADV infection...
October 2016: Medicine (Baltimore)
Anliang Huang, Dan Yue, Danying Liao, Liuliu Cheng, Jinhu Ma, Yuquan Wei, Aiping Tong, Ping Cheng
Arsenic trioxide (ATO) has demonstrated clinical efficacy in acute promyelocytic leukemia (APL) and in vitro activity in various solid tumors. As2O3 as single agent exhibits poor efficacy for treatment of hepatocellular carcinoma (HCC) in phase II trial, suggesting that new modalities of treatment with enhanced therapeutic effect and alleviated toxicity are needed for application of As2O3 on patients with HCC. Survivin is the strongest inhibitor of apoptosis protein over-expressed in tumors, which has been proposed as an attractive target for new anticancer interventions...
October 11, 2016: Oncology Reports
Yuan-Yuan Zhang, Si-Han Huang, Hua-Rong Zhou, Cong-Jie Chen, Li-Hong Tian, Jian-Zhen Shen
HOX antisense intergenic RNA (HOTAIR), a long non-coding RNA, plays an important role in the development of many types of cancers. Its function in acute leukemia (AL), however, has not been examined. The present study investigated the role of HOTAIR and its downstream genes in AL, and determined whether it could act as a molecular marker for prediction of leukemia development and prognosis. Real-time quantitative PCR was used to examine the expression of each gene in the HOTAIR signaling pathway in AL patients...
October 4, 2016: Oncology Reports
Junhui Zhou, Yidi Wu, Changrong Wang, Qiang Cheng, Shangcong Han, Xiaoxia Wang, Jianhua Zhang, Liandong Deng, Deyao Zhao, Lili Du, Huiqing Cao, Zicai Liang, Yuanyu Huang, Anjie Dong
The extremely low efficient cytosolic release of the internalized siRNA has emerged recently as a central issue for siRNA delivery, while there is a lack of guidelines to facilitate the cytosolic release of internalized siRNA. To address these concerns, we studied the contribution of the pH-sensitive inner core on handling the cytosolic release of siRNA delivered by a series of PG-P(DPAx-co-DMAEMAy)-PCB amphiphilic polycation nanomicelles (GDDC-Ms) with extremely low internalization (<1/4 of lipofactamine 2000 (Lipo2000))...
October 17, 2016: Nano Letters
J Kanda, Y Morishima, S Terakura, A Wake, N Uchida, S Takahashi, Y Ono, Y Onishi, H Kanamori, N Aotsuka, Y Ozawa, H Ogawa, T Sakura, K Ohashi, T Ichinohe, K Kato, Y Atsuta, T Teshima, M Murata
The effect of graft-versus-host disease (GVHD) on transplant outcomes after unrelated cord blood transplantation (UCBT) has not been fully elucidated. We analyzed the impact of acute and chronic GVHD on outcomes in adult patients with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n=2558). The effect of GVHD on outcomes was analyzed after adjusting for other significant variables. The occurrence of GVHD was treated as a time-dependent covariate. The occurrence of grade 1-2 or 3-4 acute GVHD was significantly associated with a lower relapse rate...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
J Xin, D You, P Breslin, J Li, J Zhang, W Wei, J Cannova, A Volk, R Gutierrez, Y Xiao, A Ni, G Ng, R Schmidt, Z Xia, J Pan, H Chen, M M Patel, P C Kuo, S Nand, A R Kini, J Zhang, J Chen, J Zhu, J Zhang
Tumor necrosis factor-α (TNF)-induced RIP1/RIP3-mediated necroptosis has been proposed to be an alternative strategy for treating apoptosis-resistant leukemia. However, we found that most acute myeloid leukemia (AML) cells, especially M4 and M5 subtypes, produce TNF and show basal level activation of RIP1/RIP3/MLKL signaling, yet do not undergo necroptosis. TNF, through RIP1/RIP3 signaling, prevents degradation of SOCS1, a key negative regulator of interferon-γ (IFN-γ) signaling. Using both pharmacologic and genetic assays, we show here that inactivation of RIP1/RIP3 resulted in reduction of SOCS1 protein levels and partial differentiation of AML cells...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
M Wu, M Hamaker, L Li, D Small, A S Duffield
The FMS-like tyrosine kinase-3 (FLT3) gene is the most commonly mutated gene in acute myeloid leukemia (AML), and patients carrying internal tandem duplication (ITD) mutations have a poor prognosis. Long-term inhibition of FLT3 activity in these patients has been elusive. To provide a more complete understanding of FLT3 biology, a mass spectroscopy-based screen was performed to search for FLT3-interacting proteins. The screen identified dedicator of cytokinesis 2 (DOCK2), which is a guanine nucleotide exchange factor for Rho GTPases, and its expression is limited to hematolymphoid cells...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Elisabetta Zappone, Marzia Defina, Lara Aprile, Alessandro Gozzetti, Giulia Bartalucci, Monica Bocchia
In recent years there has been a great improvement in molecular characterization of acute myeloid leukemia (AML) allowing the stratification of patients in different rate of risk. Patients with FLT3 mutated AML have poor prognosis because of resistance to induction chemotherapy or early relapse. Several first and second generation molecules, able to inhibit FLT3 signaling have been developed and many single agent or combination studies are ongoing. Of these, quizartinib seems to have the best clinical activity...
October 10, 2016: Anti-cancer Agents in Medicinal Chemistry
Patrice Chevallier, Myriam Labopin, Regis Peffault de La Tour, Bruno Lioure, Claude-Eric Bulabois, Anne Huynh, Didier Blaise, Pascal Turlure, Etienne Daguindau, Natacha Maillard, Ibrahim Yakoub-Agha, Gaelle Guillerm, Jeremy Delage, Nathalie Contentin, Jacques-Olivier Bay, Florence Beckerich, Jean-Henri Bourhis, Marie Detrait, Stéphane Vigouroux, Sylvie François, Faezeh Legrand, Thierry Guillaume, Mohamad Mohty
We have retrospectively compared survivals between acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients who received either a clofarabine/busulfan (CloB2A2) or a fludarabine/busulfan (FB2A2) RIC regimen for allogeneic stem cell transplantation. Between 2009 and 2014, 355 allotransplanted cases were identified from the SFGM-TC registry as having received either the FB2A2 (n = 316, 56% males, median age: 59.2 years, AML 78.5%, first complete remission [CR1] 72%, median follow-up: 20 months) or the CloB2A2 (n = 39, 62% males, median age: 60...
October 17, 2016: Cancer Medicine
Mervi Taskinen, Trausti Oskarsson, Mette Levinsen, Matteo Bottai, Marit Hellebostad, Olafur Gisli Jonsson, Päivi Lähteenmäki, Kjeld Schmiegelow, Mats Heyman
BACKGROUND: Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy. PROCEDURES: Retrospectively, we estimated the effect of CNS involvement and CNS-RT on events and overall survival (OS) in 835 children treated for high-risk ALL in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000 trials...
October 17, 2016: Pediatric Blood & Cancer
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