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Leukemia Research

Eric Gars, Satinder Kaur, Daniel Thomas
No abstract text is available yet for this article.
November 1, 2018: Leukemia Research
Paolo Gallipoli
No abstract text is available yet for this article.
October 24, 2018: Leukemia Research
Prisca M J Theunissen, Maaike de Bie, David van Zessen, Valerie de Haas, Andrew P Stubbs, Vincent H J van der Velden
Antigen receptor gene rearrangements are frequently applied as molecular targets for detection of minimal residual disease (MRD) in B-cell precursor acute lymphoblastic leukemia patients. Since such targets may be lost at relapse, appropriate selection of antigen receptor genes as MRD-PCR target is critical. Recently, next-generation sequencing (NGS) - much more sensitive and quantitative than classical PCR-heteroduplex approaches - has been introduced for identification of MRD-PCR targets. We evaluated 42 paired diagnosis-relapse samples by NGS (IGH, IGK, TRG, TRD, and TRB) to evaluate clonal evolution patterns and to design an algorithm for selection of antigen receptor gene rearrangements most likely to remain stable at relapse...
October 22, 2018: Leukemia Research
Laleh S Arabanian, Pegah Johansson, Anna Staffas, Tina Nilsson, Arefeh Rouhi, Linda Fogelstrand, Lars Palmqvist
Endothelin receptor type A (EDNRA) is known as a mediator of cell proliferation and survival. Aberrant regulation of EDNRA has been shown to play a role in tumor growth and metastasis. Using a global gene expression screen, we found that expression of Ednra was upregulated in murine leukemia inducing cells co-expressing Hoxa9 and Meis1 compared to cells only expressing Hoxa9. The aim of this study was to explore the role of Ednra in leukemogenesis further. In a murine bone marrow transplantation model, mice transplanted with cells overexpressing Ednra and Hoxa9 succumbed to leukemia significantly earlier than mice transplanted with cells overexpressing Hoxa9 only...
October 13, 2018: Leukemia Research
Gunnar Birgegård, Folke Folkvaljon, Hans Garmo, Lars Holmberg, Carlos Besses, Martin Griesshammer, Luigi Gugliotta, Jingyang Wu, Heinrich Achenbach, Jean-Jacques Kiladjian, Claire N Harrison
EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both. At registration, 481 patients had ANA treatment without HC exposure, 2305 had HC without ANA exposure, and 674 had been exposed to both...
October 11, 2018: Leukemia Research
Yoo-Jin Kim, Seung-Hyun Jung, Eun-Hye Hur, Eun-Ji Choi, Kyoo-Hyung Lee, Seon-Hee Yim, Hye-Jung Kim, Yong-Rim Kwon, Young-Woo Jeon, Sug Hyung Lee, Yeun-Jun Chung, Je-Hwan Lee
We investigated the prognostic role of somatic mutations in allogeneic hematopoietic cell transplantation (HCT) for de novo myelodysplastic syndrome (MDS). We performed targeted deep sequencing analysis of 26 genes on bone marrow samples obtained within 6 weeks before HCT from 202 patients with de novo MDS. Overall, 76% of patients carried one or more somatic mutations, and TP53 mutation was present in 23 patients (11.4%). Overall survival (OS) at 5 years was 63.6%, cumulative incidence of relapse (CIR) was 18...
October 11, 2018: Leukemia Research
Cora Hallas, Michael Preukschas, Markus Tiemann
Gene expression profiling (GEP) separated diffuse large B-cell lymphoma (DLBCL) in two different entities, i.e. activated B cell-like (ABC) and germinal center B cell-like (GCB) lymphomas with ABC lymphomas demonstrating a less favorable outcome. NF-kB pathway activating mutations in MYD88, CD79A/B and CARD11 are predominantly found in ABC type lymphomas. Targeted therapies affecting NF-kB pathways have shown therapeutic potential in this subtype. Immunohistochemistry algorithms have been developed as a tool for distinguishing these entities in routine clinical diagnostics...
October 10, 2018: Leukemia Research
Kendra Sweet, Lori Hazlehurst, Eva Sahakian, John Powers, Lisa Nodzon, Fadi Kayali, Kelly Hyland, Ashley Nelson, Javier Pinilla-Ibarz
PURPOSE: Preclinical evidence indicates that the bone marrow microenvironment provides a protective niche for leukemic stem cells, allowing them to evade the effects of BCR-ABL tyrosine kinase inhibitors (TKIs), but that targeting of the JAK-STAT pathway with the JAK2 inhibitor ruxolitinib increases TKI-induced apoptosis. A phase I clinical trial (NCT01702064) investigated the tolerability and safety of treating chronic-phase chronic myeloid leukemia patients with ruxolitinib in combination with the BCR-ABL TKI nilotinib and explored initial efficacy evidence...
October 9, 2018: Leukemia Research
Francesca Palandri, Giuseppe A Palumbo, Massimiliano Bonifacio, Massimo Breccia, Roberto Latagliata, Bruno Martino, Nicola Polverelli, Elisabetta Abruzzese, Mario Tiribelli, Maura Nicolosi, Micaela Bergamaschi, Alessia Tieghi, Alessandra Iurlo, Nicola Sgherza, Francesco Cavazzini, Alessandro Isidori, Gianni Binotto, Adalberto Ibatici, Monica Crugnola, Florian Heidel, Costanza Bosi, Daniela Bartoletti, Giuseppe Auteri, Lucia Catani, Antonio Cuneo, Franco Aversa, Gianpietro Semenzato, Michele Cavo, Nicola Vianelli, Giulia Benevolo
No abstract text is available yet for this article.
October 5, 2018: Leukemia Research
Massimiliano Bonifacio, Luigi Scaffidi, Gianni Binotto, Maria Cristina Miggiano, Marco Danini, Claudia Minotto, Davide Griguolo, Luciana Marin, Luca Frison, Fabio D'Amore, Marco Basso, Roberto Sartori, Martina Tinelli, Manuela Stulle, Stefania Fortuna, Angela Bonalumi, Giovanni Bertoldero, Ercole De Biasi, Marco Ruggeri, Gianpietro Semenzato, Renato Fanin, Giovanni Pizzolo, Mauro Krampera, Mario Tiribelli
The use of generic drugs after patent expiration of their originators is a relative novelty in the treatment of chronic cancer patients in Western countries. In this observational study we analyzed a cohort of 294 Italian chronic phase chronic myeloid leukemia patients treated frontline with branded imatinib (Glivec®) for at least 6 months and then uniformly switched to generic imatinib upon requirement of health authorities in early 2017. Median age at diagnosis was 57 years (range 19-87). Sokal risk was low/intermediate/high in 55%, 32% and 8% of cases, respectively...
October 2, 2018: Leukemia Research
Yimamu Maimaitili, Aki Inase, Yoshiharu Miyata, Akihito Kitao, Yu Mizutani, Seiji Kakiuchi, Yohei Shimono, Yasuyuki Saito, Takashi Sonoki, Hironobu Minami, Hiroshi Matsuoka
Gemtuzumab ozogamicin (GO), the first antibody-drug conjugate (ADC), has attracted the interest of hematologists because more than 90% of acute myeloid leukemia (AML) blasts express its target, CD33. Although GO and subsequently developed ADCs depend on lysosomes for activation, lysosome number and activity in tumor cells has not been well elucidated. In this study, we investigated whether an mTORC1/2 kinase inhibitor, PP242, which was reported to activate lysosomal function, potentiates the cytotoxicity of GO in AML cells...
October 2, 2018: Leukemia Research
Kotaro Hishiki, Masaharu Akiyama, Yumi Kanegae, Koji Ozaki, Miyuki Ohta, Emi Tsuchitani, Ken Kaito, Hisashi Yamada
Novel epigenetic therapies targeting bromodomain and extra-terminal (BET) family proteins have shown therapeutic efficacy in diverse hematologic malignancies and solid cancers. However, the mechanism of resistance remains poorly understood. In the present study, we evaluated the mechanism of resistance to the BET inhibitor I-BET151 and its signaling pathway to overcome resistance in U937 cells. Treatment with 10 μM I-BET151 significantly induced growth inhibition, apoptosis, and cell cycle modulation, including increases in sub-G1 and G1 phases and decreases in S and G2/M phases, in U937 cells...
October 2, 2018: Leukemia Research
Mei-Ling Chong, Hao Cheng, Peisong Xu, Hong You, Min Wang, Lu Wang, Hao-Han Ho
No abstract text is available yet for this article.
September 29, 2018: Leukemia Research
Omer Jamy, Sejong Bae, Luciano J Costa, Harry P Erba, Nikolaos Papadantonakis
BACKGROUND: Patients with acute myeloid leukemia (AML) treated with intensive chemotherapy may require re-induction based on the evaluation of day 14 bone marrow biopsy. METHODS: A retrospective chart review was performed to evaluate adult patients with AML who received re-induction with fludarabine, high dose cytarabine and granulocyte colony stimulating factor (FLAG) regimen for residual disease (≥ 5% blasts by morphology) on day 14 bone marrow examination between September 2012 and July 2017 at our institution...
September 27, 2018: Leukemia Research
María Sol Brassesco, Julia Alejandra Pezuk, Maria Angelica Cortez, Karina Bezerra Salomão, Carlos Alberto Scrideli, Luiz Gonzaga Tone
PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, and despite the high rate of cure (over 80%) it still has a big impact on morbidity and mortality. The Transducin-like enhancer of split 1 (TLE1), a transcriptional corepressor, has been described as dysregulated and recently emerged as a tumor marker in several cancer types, including hematologic malignancies. METHODS: In the present study TLE1 gene expression was evaluated by RT-qPCR...
September 26, 2018: Leukemia Research
Yuka Nakamura, Motoshi Ichikawa, Hideaki Oda, Ieharu Yamazaki, Ko Sasaki, Kinuko Mitani
The RUNX1-EVI1 gene generated by the t(3;21) translocation encodes a chimeric transcription factor and is a causative gene in the development of de novo acute megakaryoblastic leukemia and leukemic transformation of hematopoietic stem cell tumors. Heterozygous RUNX1-EVI1 knock-in mice die in utero due to hemorrhage in the central nervous system and spinal cord and complete abolishment of definitive hematopoiesis in the fetal liver. On the other hand, the chimeric knock-in mouse develops acute megakaryoblastic leukemia...
September 26, 2018: Leukemia Research
Chunyan Li, Xuejun Ma, Ziqiang Pan, Fangfang Lv, Zuguang Xia, Kai Xue, Qunling Zhang, Dongmei Ji, Junning Cao, Xiaonan Hong, Ye Guo
The standard treatment of waldeyer's ring DLBCL remains controversial. This retrospective study was designed to evaluate the role of consolidation radiotherapy (RT) in patients with stage I/II diffuse large B-cell lymphoma (DLBCL) limited in Waldeyer's ring (WR). We included 72 patients, 42 were treated with immunochemotherapy alone (CT group) and 30 were treated with immunochemotherapy followed by radiotherapy (CT + RT group). All patients received at least 3 cycles of R-CHOP regimen and achieved complete remission (CR) after immunochemotherapy...
September 24, 2018: Leukemia Research
Katie Podshivalova, Eileen A Wang, Traver Hart, Daniel R Salomon
miR-150 functions as a tumor suppressor in malignancies of the lymphocyte lineage and its expression is significantly reduced in these cells. However, the mechanism of miR-150 repression is unknown and so are pharmacological interventions that can reverse it. Here, we report that reduced expression of miR-150 in human Jurkat T-cell acute lymphoblastic leukemia (T-ALL) cells is mediated by constitutive mTOR signaling, a common characteristic of T-ALL cell lines and clinical isolates. Activating mTOR signaling in non-malignant T cells also resulted in a significant miR-150 down-regulation...
September 22, 2018: Leukemia Research
Andrew M Brunner, Peter Geon Kim, Hossein Sadrzadeh, Benjamin J Drapkin, Kellie A Sprague, J Mark Sloan, Wanxing Chai-Ho, Parul Bhargava, Olga Pozdnyakova, Amir T Fathi
No abstract text is available yet for this article.
September 19, 2018: Leukemia Research
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