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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
Mixue Xie, Qi Jiang, Li Li, Jingjing Zhu, Lixia Zhu, De Zhou, Yanlong Zheng, Xiudi Yang, Mingyu Zhu, Jianai Sun, Wanzhuo Xie, Xiujin Ye
BACKGROUND: In China, the combination of homoharringtonine, cytarabine, and G-CSF (HAG) has been extensively applied for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: We performed a meta-analysis of 2,314 patients (AML, n = 1754; MDS, n = 560) to determine the overall safety and efficacy of this regimen. RESULTS: The complete response (CR) rate of AML patients (53%) was significantly higher than that of MDS/transformed-AML patients (45%; P = 0...
2016: PloS One
Ting Yang, Qiaoxian Lin, Jinhua Ren, Ping Chen, Xiaohong Yuan, Xiaofeng Luo, Tingbo Liu, Jing Zheng, Zhihong Zheng, Xiaoyun Zheng, Xinji Chen, Langhui Zhang, Hao Zheng, Zaisheng Chen, Xueling Hua, Shaohua Le, Jian Li, Zhizhe Chen, Jianda Hu
Haplo-HSCT has been used when HLA-matched siblings are not available. Conditioning regimens aim to reduce tumor burden prior to HSCT and provide sufficient immunoablation. We report the outcome of haplo-HSCT in 63 consecutive patients from 2/2013 to 12/2015 (19 females/44 males) with high-risk or relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5-advanced-MDS; 2-CML-BC). Median age was 20 years (range: 1.1-49). Twenty-one patients achieved remission prior to transplant, while 42 did not...
October 1, 2016: Oncotarget
Joanna E Drozd-Sokołowska, Krzysztof Mądry, Anna Waszczuk-Gajda, Tomasz Żóltak, Anna Sikorska, Andrzej Mital, Jarosław Wajs, Grażyna Semeńczuk, Anna Szmigielska-Kapłon, Magdalena Szczepańska, Ewa Wasilewska, Paweł Szwedyk, Jadwiga Hołojda, Marzena Wątek, Beata Stella-Hołowiecka, Maria Soroka-Wojtaszko, Wojciech Homenda, Mirosław Polak, Renata Guzicka-Kazimierska, Agnieszka Porowska, Wiesław Wiktor-Jędrzejczak, Jadwiga Dwilewicz-Trojaczek
OBJECTIVES: The epidemiology of myelodysplastic syndromes (MDS) differs among countries. Here we present the first epidemiological indices determined for Poland. METHODS: 21 haematological centres participated in the study. Patients diagnosed with MDS and acute myeloid leukaemia (AML) with 20-29% blasts were enrolled. Data collection was conducted for strictly predefined period. RESULTS: The overall crude incidence rate for all MDS subtypes was 1...
October 4, 2016: European Journal of Haematology
Marios Dimitriou, Petter S Woll, Teresa Mortera-Blanco, Mohsen Karimi, David C Wedge, Helen Doolittle, Iyadh Douagi, Elli Papaemmanuil, Sten Eirik W Jacobsen, Eva Hellström-Lindberg
The stem and progenitor cell compartments in low- and intermediate-risk myelodysplastic syndromes (MDS) have recently been described, and shown to be highly conserved when compared to those in acute myeloid leukemia (AML). Much less is known about the characteristics of the hematopoietic hierarchy of subgroups of MDS with a high risk of transforming to AML. Immunophenotypic analysis of immature stem and progenitor cell compartments from patients with an isolated loss of the entire chromosome 7 (isolated -7), an independent high-risk genetic event in MDS, showed expansion and dominance of the malignant -7 clone in the granulocyte and macrophage progenitors (GMP), and other CD45RA+ progenitor compartments, and a significant reduction of the LIN-CD34+CD38low/-CD90+CD45RA- hematopoietic stem cell (HSC) compartment, highly reminiscent of what is typically seen in AML, and distinct from low-risk MDS...
September 24, 2016: Oncotarget
A Stengel, W Kern, T Haferlach, M Meggendorfer, A Fasan, C Haferlach
Alterations in TP53 have been described in many cancer types including hematological neoplasms. We aimed at comparing TP53 mutations (mut) and deletions (del) in a large cohort of patients with hematological malignancies (n=3307), including AML (n=858), MDS (n=943), ALL (n=358), CLL (n=1148). Overall, alterations in TP53 were detected in 332/3307 cases (10%). The highest frequency was observed in ALL (total: 19%; mut+del: 6%; mut only: 8%; del only: 5%) and AML (total: 13%; mut+del: 5%; mut only: 7%; del only: 1%), whereas TP53 alterations occurred less frequently in CLL (total: 8%) and MDS (total: 7%)...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Lia Minculescu, Hanne Vibeke Marquart, Lone Smidstrups Friis, Soeren Lykke Petersen, Ida Schiødt, Lars Peter Ryder, Niels Smedegaard Andersen, Henrik Sengeloev
Early immune reconstitution plays a critical role in clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first lymphocytes to recover after transplantation and are considered powerful effector cells in HSCT. We aimed to evaluate the clinical impact of early NK cell recovery in T cell-replete transplant recipients. Immune reconstitution was studied in 298 adult patients undergoing HSCT for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome from 2005 to 2013...
September 21, 2016: Biology of Blood and Marrow Transplantation
Chan Kyu Kim, Dong Hoon Han, Young Seok Ji, Min Sung Lee, Chang Wook Min, Seong Kyu Park, Se Hyung Kim, Jina Yun, Hyun Jeung Kim, Kyoung Ha Kim, Kyu Taek Lee, Jong Ho Won, Dae Sik Hong, Hee Kyung Kim
Angiogenesis occurs in response to tissue ischemia and wound healing, and contributes to the pathogenesis of a variety of diseases, such as benign and malignant neoplasia. Several studies have measured bone marrow microvessel density (MVD) in MDS patients and acute myeloid leukemia (AML) patients transformed from MDS, and MVD was higher in MDS patients than controls, but was lower than in AML patients. Vascular endothelial growth factor (VEGF) is expressed in bone marrow blast cells, and an autocrine VEGF signaling mechanism has been established in MDS...
September 5, 2016: Leukemia Research
Haixia Zhou, Changcheng Zheng, Xiaoyu Zhu, Baolin Tang, Juan Tong, Xuhan Zhang, Lei Zhang, Huilan Liu, Zimin Sun
No clinical studies have investigated the role of decitabine as a part of the myeloablative conditioning regimen prior to UCBT for refractory or relapsed childhood AL in patients in NR status. The aim of this study was to identify the potential benefits of decitabine as a prior therapy before salvaged unrelated UCBT for refractory or relapsed childhood AL. Eight consecutive patients with childhood refractory/relapsed AL were enrolled in our study between 2013 and 2014. All patients were in NR status before the time of transplant and had features associated with poor outcomes, such as CNSL, MDS-AML, high WBC count at diagnosis, and hypodiploid status (FLT3+/ITD+)...
September 12, 2016: Pediatric Transplantation
Marie Toft-Petersen, Line Nederby, Eigil Kjeldsen, Gitte B Kerndrup, Gordon D Brown, Peter Hokland, Anne Stidsholt Roug
Evidence of distinct disease propagating stem cells in myelodysplastic syndrome (MDS) has emerged in recent years. However, immunophenotypic characterization of these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have previously described aberrant expression of the C-type lectin domain family 12, member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a tool for assessing minimal residual disease. Furthermore, CLEC12A has been proposed as a promising marker of leukaemic stem cells in AML...
September 9, 2016: British Journal of Haematology
Jenny N Poynter, Michaela Richardson, Michelle Roesler, Cindy K Blair, Betsy Hirsch, Phuong Nguyen, Adina Cioc, James R Cerhan, Erica Warlick
Benzene exposure is one of the few well-established risk factors for myeloid malignancy. Exposure to other chemicals has been inconsistently associated with hematologic malignancies. We evaluated occupational and residential chemical exposures as risk factors for AML and MDS using population-based data. AML and MDS cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota driver's license/identification card list. Chemical exposures were measured by self-report...
September 7, 2016: International Journal of Cancer. Journal International du Cancer
Sweta Shah, Jennifer Hankenson, Smitha Pabbathi, John Greene, Sowmya Nanjappa
OBJECTIVE: Clostridium tertium is considered an uncommon pathogen in humans, but is a cause of bacteremia in patients with underlying hematological malignancies and neutropenia. A case series highlighting 10 years of experience with C. tertium as a cause of bacteremia in this population is presented; the cases were seen at a National Cancer Institute designated cancer center. METHODS: Institutional review board approval was obtained prior to the start of the study...
August 26, 2016: International Journal of Infectious Diseases: IJID
Didem Ozkazanc, Digdem Yoyen-Ermis, Ece Tavukcuoglu, Yahya Buyukasik, Gunes Esendagli
To cope with immune responses, tumor cells implement elaborate strategies such as adaptive resistance and induction of T cell exhaustion. T cell exhaustion has been identified as a state of hyporesponsiveness that arises under continuous antigenic stimulus. Nevertheless, contribution of costimulatory molecules to T cell exhaustion in cancer remains to be better defined. This study explores the role of myeloid leukemia-derived costimulatory signals on CD4(+) helper T (Th) cell exhaustion which may limit anti-tumor immunity...
August 27, 2016: Immunology
Yan Jiang, Yanping Zhu, Zhi-Jie Liu, Songying Ouyang
RNA helicases are involved in almost every aspect of RNA, from transcription to RNA decay. DExD/H-box helicases comprise the largest SF2 helicase superfamily, which are characterized by two conserved RecA-like domains. In recent years, an increasing number of unexpected functions of these proteins have been discovered. They play important roles not only in innate immune response but also in diseases like cancers and chronic hepatitis C. In this review, we summarize the recent literatures on one member of the SF2 superfamily, the DEAD-box protein DDX41...
August 9, 2016: Protein & Cell
Wenli Zuo, Sa A Wang, Courtney DiNardo, Mariko Yabe, Shaoying Li, L Jeffrey Medeiros, Guilin Tang
AIMS: Chromosome 11q23 translocations, resulting in MLL (KMT2A) rearrangement, have been well characterised in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). However, little is known of haematopoietic neoplasms associated with 11q23 translocation but without MLL rearrangement (11q23+/MLL-). The aim of this study is to characterise such cases with 11q23+/MLL-. METHODS AND RESULTS: We retrospectively searched our database for cases with haematopoietic malignancies with 11q23+/MLL-...
August 5, 2016: Journal of Clinical Pathology
Xin Zhao, Xin Tian, Sachiko Kajigaya, Caroline R Cantilena, Stephen Strickland, Bipin N Savani, Sanjay Mohan, Xingmin Feng, Keyvan Keyvanfar, Neil Dunavin, Danielle M Townsley, Bogdan Dumitriu, Minoo Battiwalla, Katayoun Rezvani, Neal S Young, A John Barrett, Sawa Ito
Although recent observations implicate the importance of telomerase activity in acute myeloid leukaemia (AML), the roles of epigenetic regulations of the TERT gene in leukaemogenesis, drug resistance and clinical prognosis in AML are not fully understood. We developed a quantitative pyrosequencing-based methylation assay covering the TERT proximal promoter and a partial exon 1 (TERTpro/Ex1) region and tested both cell lines and primary leukaemia cells derived from AML and AML with preceding myelodysplastic syndrome (AML/MDS) patients (n = 43)...
July 19, 2016: British Journal of Haematology
Ting Zhou, Stephanie N Perez, Ziming Cheng, Marsha C Kinney, Madeleine E Lemieux, Linda M Scott, Vivienne I Rebel
Perturbations in CREB binding protein (CREBBP) are associated with hematopoietic malignancies, including myelodysplastic syndrome (MDS). Mice hemizygous for Crebbp develop myelodysplasia with proliferative features, reminiscent of human MDS/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U), and a proportion goes on to develop acute myeloid leukemia (AML). We have also shown that the Crebbp+/- non-hematopoietic bone marrow microenvironment induces excessive myeloproliferation of wild-type cells. We now report that transplantation of unfractionated Crebbp+/- bone marrow into wild-type recipients resulted in either early-onset AML or late-onset MDS and MDS/MPN-U...
2016: PloS One
Sebastián Ortiz, Maria T Orero, Karla Javier, Carolina Villegas, Irene Luna, Pedro Pérez, Mónica Roig, María López, Sofía Costa, Félix Carbonell, Rosa Collado, David Ivars, Mariano Linares
BACKGROUND: The incidence of alloimmunisation in myelodysplastic syndromes (MDS) during the era of supportive treatment ranges from 9 to 56%. However, it is unknown if the widespread use of hypomethylating agents has changed the risk of immunisation. The aim of this study is to evaluate the impact of azacitidine (AZA) therapy on red blood cell (RBC) alloimmunisation in transfused patients with MDS, myelodysplastic syndromes/myeloproliferative syndromes (MDS/MPS) and secondary acute myeloid leukaemia (AML)...
June 24, 2016: Blood Transfusion, Trasfusione del Sangue
Marc De Braekeleer, Nathalie Douet-Guilbert, Etienne De Braekeleer
The p15 gene (also known as CDKN2B, INK4B, p15(INK4B)), located in band 9p21, encodes a protein that induces a G1-phase cell cycle arrest through inhibition of CDK4/6 (cyclin-dependent kinase 4/6). It also plays an important role in the regulation of cellular commitment of hematopoietic progenitor cells and myeloid cell differentiation. p15 can be silenced by several mechanisms, including deletion and hypermethylation of its promoter. Homozygous p15 deletion is rare in acute myeloblastic leukemia (AML) and myelodysplastic syndromes (MDS) but frequent in acute lymphoblastic leukemia (ALL)...
July 12, 2016: Leukemia & Lymphoma
Astrid Olsnes Kittang, Kristoffer Sand, Annette Katharina Brenner, Kristin Paulsen Rye, Øystein Bruserud
INTRODUCTION: Myelodysplastic syndromes (MDS) are characterized by bone marrow failure due to disturbed bone marrow maturation. MDS is associated with increased risk of transformation to acute myeloid leukemia (AML) and features of immunological dysregulation. MATERIALS AND METHODS: Serum levels of 47 soluble immune mediators were examined in samples derived from 49 MDS patients (35 low-risk and 14 high-risk) and 23 healthy adults. Our patients represent an unselected population-based cohort...
2016: International Journal of Molecular Sciences
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