Germline CEBPA mutations in Korean patients with acute myeloid leukemia
CCAAT/enhancer binding protein alpha (CEBPA) mutations occur in 7.5% to 12.8% of de novo acute myeloid leukemia (AML) [1 –4]. Two types of mutations are possible: an N-terminal frame-shift mutation causing a 42-kDa isoform truncation and 30-kDa isoform overproduction and a C-terminal in-frame mutation in the basic leucine zipper (bZIP) region disrupting the DNA binding and dimerization of CEBPA . CEBPA double mut ations (CEBPAdm) usually contain an N-terminal and a C-terminal mutation, which is now known to be a favorable prognostic factor . (Source: Leukemia Research)
Source: Leukemia Research - December 11, 2018 Category: Hematology Authors: Hoon Seok Kim, Eunhee Han, Woori Jang, Myungshin Kim, Yonggoo Kim, Kyungja Han, Hee-Je Kim, Bin Cho Tags: Letter to the Editor Source Type: research
The management and outcomes of patients with myelodysplastic syndrome with persistent severe thrombocytopenia: An observational single centre registry study
Thrombocytopenia (platelets (Source: Leukemia Research)
Source: Leukemia Research - December 10, 2018 Category: Hematology Authors: Abi Vijenthira, Devyani Premkumar, Jeannie Callum, Yulia Lin, Richard A. Wells, Lisa Chodirker, Martha Lenis, Alexandre Mamedov, Rena Buckstein Tags: Research paper Source Type: research
Comparison of 18f fdg pet-ct and cect in pretreatment staging of adults with hodgkin ’s lymphoma
Hodgkin Lymphoma (HL) is a chemo-radiosensitive cancer with a five-year survival rate over 85% with current therapies . However, there are serious long-term therapy related adverse events such as second cancers, cardiac and peripheral vascular disease, pulmonary disease, infertility, sexual dysfunction, etc. Therefore, it is extremely important to reduce the long-term side effects, reducing the amount and toxicity of poly-chemotherapies and improving staging procedures [2,3]. (Source: Leukemia Research)
Source: Leukemia Research - December 5, 2018 Category: Hematology Authors: Martina Panebianco, Oreste Bagni, Natalia Cenfra, Sergio Mecarocci, Elettra Ortu La Barbera, Luca Filippi, Giovanni Codacci-Pisanelli, Tommaso Biondi, Andrea Laghi, Giuseppe Cimino Tags: Research paper Source Type: research
Deferasirox in the treatment of iron overload during myeloproliferative neoplasms in fibrotic phase: does ferritin decrement matter?
Iron overload is a well-known critical issue in transfusion dependent patients affected by chronic hematological diseases, as thalassemic syndromes (TS)1ormyelodisplastic syndromes (MDS)2.Excess iron can be extremely toxic may cause organ damage in the absence of iron chelation therapy. Preclinical studies on the role of free iron toxicity on bone marrow function have shown that this condition leads to an accumulation of reactive oxygen species, interfers with the expression of genes encoding for hematopoiesis regulating proteins, and inhibits hematopoiesis. (Source: Leukemia Research)
Source: Leukemia Research - December 4, 2018 Category: Hematology Authors: Ambra Di Veroli, Alessia Campagna, Marianna De Muro, Malgorzata Monika Trawinska, Sabrina LeonettiCrescenzi, Luca Petriccione, Atelda Romano, Ada D ’Addosio, Antonia Cenfra, Marco Montanaro, Stefano Felici, Alessandro Andriani, Ida Carmosino, Pasquale N Tags: Research paper Source Type: research
MDS-associated mutations in germline GATA2 mutated patients with hematologic manifestations
GATA2 is a zinc finger transcription factor important for the production and maintenance of hematopoietic stem cells both in the embryo and during adult definitive hematopoiesis. It activates its own expression and thus hematopoietic cells are extremely sensitive the levels of GATA2 . GATA2 binds to several downstream targets including SPI1 (PU.1), LMO2, TAL1, FLI1 and RUNX1 . In humans, germline mutations have been shown to be the cause of the disorder known as GATA2 deficiency. Mutations across the gene, including missense, frameshift, nonsense, deletions, and regulatory variants lead to haploinsufficiency and dise...
Source: Leukemia Research - December 4, 2018 Category: Hematology Authors: Lisa J. McReynolds, Yanqin Yang, Hong Yuen Wong, Jingrong Tang, Yubo Zhang, Matthew P. Mul é, Janine Daub, Cindy Palmer, Ladan Foruraghi, Qingguo Liu, Jun Zhu, Weixin Wang, Robert R. West, Marielle E. Yohe, Amy P. Hsu, Dennis D. Hickstein, Danielle M. To Tags: Research paper Source Type: research
Hepatic and cardiac and iron overload detected by T2* magnetic resonance (MRI) in patients with myelodisplastic syndrome: a cross-sectional study
Myelodysplastic syndrome (MDS) is a heterogeneous group of disorders characterized by clonal, dysplastic, ineffective hematopoiesis and an increased propensity to develop acute myeloid leukemia (AML) . Approximately 60% to 80% of patients with MDS experience symptomatic anemia, and 40% to 50% may develop transfusion-dependent anemia. Transfusion-dependent anemia is associated with the development of iron overload and decreased survival. However, iron overload may occur before patients become transfusion-dependent, since ineffective erythropoiesis suppress hepcidin production in the liver and may lead to increased iron a...
Source: Leukemia Research - December 4, 2018 Category: Hematology Authors: Luiz Fernando Mantovani, Fabio Pires de Souza Santos, Guilherme Fleury Perini, Claudia Mac-Donald Bley do Nascimento, Leandro de P ádua Silva, Carolina Kassab Wroclawski, Breno Pannia Esposito, Murilo Sérgio Sardo Ribeiro, Elvira Deolinda Rodrigues Pere Tags: Research paper Source Type: research
Impact of NPM1 mutation subtypes on treatment outcome: the Lyon-University Hospital experience
The nucleophosmin member 1 (NPM1) is an abundant multifunctional nucleolar protein involved in the maintenance of genome stability and ribosome biogenesis . Mutations in the NPM1gene are detected in approximately one-third of all patients with acute myeloid leukemia (AML) and up to 60% of those with normal cytogenetics . The gene encoding NPM1 is located on 5q35.1 and contains 12 exons. NPM1 is involved in epigenetic control, ribosomal protein assembly, and regulation of p53 tumor suppressor pathway . (Source: Leukemia Research)
Source: Leukemia Research - November 29, 2018 Category: Hematology Authors: Ma ël Heiblig, Pierre Sujobert, Sandrine Hayette, Marie Balsat, Mohamed Elhamri, Gilles Salles, Xavier Thomas Tags: LETTER TO THE EDITOR Source Type: research
Ocular Manifestations in Acute Lymphoblastic Leukemia: A Five-Year Cohort Study of Pediatric Patients
Ocular manifestations in Acute Lymphoblastic Leukemia (ALL), varying from 43% to 90% depending on the study, are concerning because they are often silent [1,2]. Such manifestations often go unperceived since most patients are asymptomatic. Nevertheless, they can indicate a relapse or early worsening of the condition with a potential risk to the patient ’s sight. (Source: Leukemia Research)
Source: Leukemia Research - November 29, 2018 Category: Hematology Authors: Cristiano de Queiroz Mendon ça, Marcelle Vieira Freire, Simone Santana Viana, Mayo Kayann Guerra Silva Tavares, Wallace Marcelo Almeida Silva, Rosana Cipolotti Source Type: research
Efficacy and toxicity of decitabine in patients with acute myeloid leukemia (aml): a multicenter real-world experience
Acute myeloid leukemia (AML) treatment options for older patients with AML either for first line or in relapsed/refractory cases are limited, with very poor outcomes (1 –3). Elderly patients are often ineligible for intensive anti-leukemic chemotherapy (CHT) or participation to clinical trial due to poor performance status and/or organ dysfunction. This population has an increased incidence of pre-existing myelodysplastic syndrome (MDS), unfavorable cytogenetics and multi-drug-resistant phenotype, any of which can impair the efficacy of intensive antileukemic CHT (1–3). (Source: Leukemia Research)
Source: Leukemia Research - November 28, 2018 Category: Hematology Authors: Carla Fil ì, Anna Candoni, Maria Elena Zannier, Jacopo Olivieri, Silvia Imbergamo, Manuela Caizzi, Gianpaolo Nadali, Eros Di Bona, Anna Ermacora, Michele Gottardi, Davide Facchinelli, Rosanna Ciancia, Davide Lazzarotto, Maria Vittoria Dubbini, Gianluca F Tags: Research paper Source Type: research
Compound mutations involving T315I and P-loop mutations are the major components of multiple mutations detected in tyrosine kinase inhibitor resistant chronic myeloid leukemia
BCR-ABL1 kinase domain mutations are a major mechanism of tyrosine kinase inhibitor (TKI) resistance in patients with chronic myeloid leukemia (CML). These mutations interfere the binding of TKIs to the binding site [1 –3]. To date, various studies have shown that some of these mutations are strongly related to clinical resistance [2–5], and the sensitivity to different TKIs is dependent on the type of mutation [6–10]. Patients with multiple mutations have poorer prognosis than patients with a single mutatio n [11,12]. (Source: Leukemia Research)
Source: Leukemia Research - November 27, 2018 Category: Hematology Authors: Ki-Hoon Kang, Soo-Hyun Kim, Soo-Young Choi, Hae-Lyun Yoo, Mi-Young Lee, Hye-Young Song, Kyung-Mi Kee, Ji-Hyung Suh, Seon-Young Yang, Eun-Jung Jang, Sung-Eun Lee, Dong-Wook Kim Tags: Research paper Source Type: research
Immunophenotypic measurable residual disease (MRD) in acute myeloid leukemia: Is multicentric MRD assessment feasible?
Acute myeloid leukemia (AML) is a heterogeneous malignant disease characterized by the accumulation of immature myeloid progenitor cells, which leads to anemia, thrombocytopenia and impaired immunity. Treatment with intensive chemotherapy regimens of adult AML patients who are 60 years of age or younger results in hematologic remission in about 70-90% of patients, but at least 30% of these patients will experience a relapse . Remaining cells in the bone marrow after chemotherapy treatment are thought to be responsible for the relapse. (Source: Leukemia Research)
Source: Leukemia Research - November 27, 2018 Category: Hematology Authors: Rik A. Brooimans, Vincent H.J. van der Velden, Nancy Boeckx, Jennita Slomp, Frank Preijers, Jeroen G. te Marvelde, Ngoc M. Van, Antoinette Heijs, Erik Huys, Bronno van der Holt, Georgine E. de Greef, Angele Kelder, Gerrit Jan Schuurhuis Tags: Research paper Source Type: research
Does Hydroxycarbamide therapy really induce leukemic transformation in patients with essential thrombocythemia?
Hydroycarbamide (HC) has been used extensively to treat patients with myeloproliferative neoplasms (MPNs) for over 4 decades. Since HC is a chemotherapeutic agent there continues to be concern that use of this agent may increase the risk of patients developing a form of acute leukemia. The BCR-ABL1-negative MPNs including polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) are clonal hematopoietic stem cell disorders which have the potential to progress to acute myeloid leukemia, termed MPN-blast phase (BP). (Source: Leukemia Research)
Source: Leukemia Research - November 22, 2018 Category: Hematology Authors: B. Marcellino, R. Hoffman, J. Mascarenhas Tags: Commentary Source Type: research
Characterization of acute myeloid leukemia with del(9q) – impact of the genes in the minimally deleted region
Acute myeloid leukemia (AML)1 arises from clonal expansion of malignant hematopoietic precursor cells of the bone marrow. The broad variety of clinical features is the result of different alterations in multiple cellular pathways. This leads to a wide range of subgroups and different treatment options. Recent studies revealed distinct molecular subgroups of AML harboring single or combined somatic mutations . The deletion of a portion of the long arm of chromosome 9, del(9q), is a recurring abnormality in malignant myeloid diseases reported in approximately 2% of AML cases . (Source: Leukemia Research)
Source: Leukemia Research - November 17, 2018 Category: Hematology Authors: Isabel S. Naarmann-de Vries, Yvonne Sackmann, Felicitas Klein, Antje Ostareck-Lederer, Dirk H. Ostareck, Edgar Jost, Gerhard Ehninger, Tim H. Br ümmendorf, Gernot Marx, Christoph Röllig, Christian Thiede, Martina Crysandt Tags: Research paper Source Type: research
In vitro stability of arsenic trioxide-liposome encapsulates for acute promyelocytic leukemia treatment
Acute promyelocytic leukemia (APL) is characterized by the t(15;17) chromosomal translocation, leading to the formation of the promyelocytic leukemia-specific-retinoic acid receptor alpha (PML-RAR α or RARA) gene and is distinguished from other forms of PML by its responsiveness to all-trans retinoic acid (ATRA, also known as Tretinoin) therapy. It is a unique subtype of APL and accounts for about 10% of all acute myeloid leukemia (AML) cases in adults . Promyelocytic leukemia was first d escribed in 1957  as a fatal illness with a median survival time of less than a week. (Source: Leukemia Research)
Source: Leukemia Research - November 16, 2018 Category: Hematology Authors: Francisco Cunha da Rosa, Renan Buque Pardinho, Mauber Eduardo Schultz Moreira, Luiz Gustavo Teixeira de Souza, Érico Marlon de Moraes Flores, Sergio Roberto Mortari, Valderi Luiz Dressler Source Type: research
An evolving technology for an evolving disease: A commentary on NGS-based MRD evaluation in B-ALL
The ability to detect “minimal residual disease” (MRD) is profoundly impacting the treatment approach to acute lymphoblastic leukemia (ALL). While several MRD assays are available, including flow cytometry and targeted PCR, “high throughput sequencing” (HTS) or next generation sequencing (NGS) methods appear part icularly promising. One of these approaches – the Adaptive Biotechnologies clonoSEQ® assay – was recently granted FDA approval. No published trial tells us what to do with knowledge of NGS-based MRD status, but clearly this is the next step. (Source: Leukemia Research)
Source: Leukemia Research - November 16, 2018 Category: Hematology Authors: Carol Fries, Richard Burack Tags: Commentary Source Type: research
Anatomical Site as a Parameter in the Predictive Model of Diffuse Large B Cell Lymphoma
Classification is essentially about prediction. Being a member of a class connotes specific qualities that are characteristic of class membership. We rely on classification to inform our thoughts and expectations. (Source: Leukemia Research)
Source: Leukemia Research - November 14, 2018 Category: Hematology Authors: David Kaplan Tags: Commentary Source Type: research
A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients
Several clinical and biological features, like cytogenetic and molecular alterations, may predict the short- and long-term outcomes in patients with AML treated with intensive approaches [1,2]. However, the main prognostic factor after front-line induction treatment is the leukemic cell sensitivity to the chemotherapy itself (i.e, to achieve or not a first CR as well as the quality and duration of the CR) [3,4]. In order to predict response to chemotherapy, many individualized sensitivity and resistance assays have been deployed for detecting ex vivo drug-inducible cell death. (Source: Leukemia Research)
Source: Leukemia Research - November 13, 2018 Category: Hematology Authors: David Mart ínez-Cuadrón, Cristina Gil, Josefina Serrano, Gabriela Rodríguez, Jaime Pérez-Oteyza, Raimundo García-Boyero, Santiago Jiménez-Bravo, Susana Vives, María Belén Vidriales, Esperanza Lavilla, José A. Pérez-Simón, Mar Tormo, Mercedes Co Source Type: research
Allogeneic hematopoietic stem cell transplantation for the treatment of BCR-ABL1-negative atypical chronic myeloid leukemia and chronic neutrophil leukemia: a retrospective nationwide study in Japan
Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are BCR-ABL1 fusion gene-negative myeloid neoplasms with an elevated number of neutrophils . Both diseases are very rare; there have been only a few cohorts of aCML patients reported, with the largest case series consisting of 65 patients [2,3], and only approximately 150 CNL cases have been reported to date . Both diseases have the overlapping clinical manifestations, such as leukocytosis, bleeding diathesis, and splenomegaly [5 –11]; and share the oncogenic-drivers and disease-modifying mutations with other myeloid neoplasms (e.g...
Source: Leukemia Research - November 12, 2018 Category: Hematology Authors: Hidehiro Itonaga, Shuichi Ota, Takashi Ikeda, Hirohumi Taji, Itsuto Amano, Yuichi Hasegawa, Tatsuo Ichinohe, Takahiro Fukuda, Yoshiko Atsuta, Akihiko Tanizawa, Takeshi Kondo, Yasushi Miyazaki Tags: Research paper Source Type: research
Systemic lupus erythematosus and lymphoma: Incidence, pathogenesis and biology
Systemic lupus erythematosus (SLE) is a multisystem auto-immune inflammatory disease, with prevalence ranging from 20-150 cases per 100,000 population . It mostly affects women of childbearing age and can involve any vital organ, in particular brain, kidneys, skin, heart and blood. SLE shows diversity, ranging from mild to potentially fatal disease mostly due to end stage organ damage . In addition to classical clinical manifestations, SLE may also present with associated co-morbidities, most significantly cardiovascular disease with accelerated atherosclerosis . (Source: Leukemia Research)
Source: Leukemia Research - November 12, 2018 Category: Hematology Authors: Alina Klein, Aaron Polliack, Anat Gafter-Gvili Source Type: research
Novel therapeutics in the treatment of hairy cell leukemia variant
Hairy cell leukemia variant (vHCL) is a B-cell lymphoproliferative disorder. The 2016 US lymphoid malignancy statistics estimate that vHCL was diagnosed in 810 patients, with an age adjusted US standard population incidence of approximately 0.2 per 100,000 . Prior to 2008, when the World Health Organization classified vHCL as a provisional diagnosis, hairy cell leukemia encompassed both classic hairy cell leukemia (cHCL) and vHCL. These two entities exhibit unique morphological, cytological and hematologic findings and are not considered to be biologically related. (Source: Leukemia Research)
Source: Leukemia Research - November 5, 2018 Category: Hematology Authors: Paul Letendre, Donald Doll Tags: Letter to the Editor Source Type: research
A clinical perspective on immunoglobulin heavy chain clonal heterogeneity in B cell acute lymphoblastic leukemia
Of the 3,100 children diagnosed with acute lymphoblastic leukemia (ALL) in the U.S. each year , approximately 10% will ultimately succumb to their disease [2,3]. Prognosis is far worse for the>3,000 U.S. adults diagnosed annually, with only about 30-40% 5-year overall survival among this cohort [4,5]. Nearly 1 in 10 adults will never even achieve remission, and more than half of those who do will go on to suffer relapse and disease-related mortality . (Source: Leukemia Research)
Source: Leukemia Research - November 3, 2018 Category: Hematology Authors: Carol Fries, W. Richard Burack Source Type: research
LMO2 functional and transcriptional regulatory profiles in hematopoietic cells
The human lmo2 gene was first cloned from acute T lymphocytic leukemia (T-ALL) patients [1,2]. It is expressed in a variety of tissues with the highest in hematopoietic stem/progenitor cells . However, LMO2 expression during thymocyte development was specifically turned off, and ectopic expression of LMO2 caused T-cell development arrest and T cell leukemia [4,5]. LMO2 consists of only two tandem LIM domains, lacks direct DNA-binding capacity and always acts as a bridging or blocking molecular via protein-protein interactions [4,6]. (Source: Leukemia Research)
Source: Leukemia Research - November 2, 2018 Category: Hematology Authors: Chao Wu, Mei Yuan, Yang Gao, Wei Sun Tags: Correspondence Source Type: research
Chemosensitivity is differentially regulated by the SDF-1/CXCR4 and SDF-1/CXCR7 axes in acute lymphoblastic leukemia with MLL gene rearrangements
Rearrangements of the mixed-lineage-leukemia (MLL) gene at chromosome 11q23 are frequently observed in infantile acute lymphoblastic leukemia (ALL) and therapy-related second leukemia [1,2], and ALL with MLL gene rearrangements (MLL+ALL) is refractory to chemotherapy and its prognosis is still dismal although it has been improved to some extent by performing hematopoietic stem cell transplantation [3,4]. Of interest, MLL+ALL has a unique gene profile clearly distinguishable from other types of ALL and acute myeloid leukemia (AML), and specific genes such as Fms-like tyrosine kinase 3 (FLT3), CD44, LMO2, and HOXA9 are overe...
Source: Leukemia Research - November 2, 2018 Category: Hematology Authors: Norie Ando, Yoshiyuki Furuichi, Shin Kasai, Minori Tamai, Daisuke Harama, Keiko Kagami, Masako Abe, Kumiko Goi, Takeshi Inukai, Kanji Sugita Tags: Research paper Source Type: research
Endothelin Receptor Emerges as a Potential Target of Hoxa9-mediated Leukemogenesis
In 2000, Padr ó et al. published a surprising finding -- bone marrow from patients with acute myeloid leukemia (AML) revealed evidence of increased angiogenesis. Microvessels staining positive for thrombomodulin and von Willebrand factor were observed at high density compared to normal bone marrow with evidence of endothelial sprouting and smaller lumens . Unexpected for a liquid tumor, this prompted further inquiry as to whether a vascular niche may be essential to support leukemic cell growth. (Source: Leukemia Research)
Source: Leukemia Research - November 1, 2018 Category: Hematology Authors: Eric Gars, Satinder Kaur, Daniel Thomas Tags: Commentary Source Type: research
The predictive value of morphological findings in early diagnosis of acute myeloid leukemia with recurrent cytogenetic abnormalities
Since the introduction of the French-American-British (FAB) morphological system, acute leukemia classifications were traditionally based on quantitative and qualitative evaluation of blast populations in bone marrow . Although revolutionary at that time, particularly in the identification of acute promyelocytic leukemia (APL), the FAB morphological system had poor reproducibility and prognostic value [2,3]. Further developments in the fields of cell immunophenotyping by flow cytometry, cytogenetic and molecular genetic analysis provided new insights into leukemia biology, opening a new era of the integrated diagnostic ...
Source: Leukemia Research - November 1, 2018 Category: Hematology Authors: Ljubomir Jakovic, Andrija Bogdanovic, Vesna Djordjevic, Marija Dencic-Fekete, Nada Kraguljac-Kurtovic, Vesna Knezevic, Natasa Tosic, Sonja Pavlovic, Tatjana Terzic Tags: Research paper Source Type: research
Hydroxyurea prior to intensive chemotherapy in AML with moderate leukocytosis
Hydroxyurea (HU) is an oral anti-proliferative drug that interferes with DNA synthesis by inhibiting ribonucleotide reductase. HU has long been used in acute myeloid leukemia (AML) for cytoreduction as part of best supportive care, or as a prephase before intensive chemotherapy in patients with an elevated white blood cell (WBC) count . A recent retrospective study showed that a pre-treatment with HU prior to intensive chemotherapy could improve short-term survival of patients with hyperleukocytic AML (HL-AML, WBC>50.109/L), but not complete remission (CR) or relapse-free survival (RFS) . (Source: Leukemia Research)
Source: Leukemia Research - October 30, 2018 Category: Hematology Authors: Sarah Bertoli, Suzanne Tavitian, Muriel Picard, Fran çoise Huguet, François Vergez, Eric Delabesse, Audrey Sarry, Emilie Bérard, Christian Récher Tags: Letter to the Editor Source Type: research
Rituximab maintenance in elderly patients with follicular lymphoma
Follicular lymphoma (FL) is a chronic, indolent lymphoid malignancy and represents the most common slow growing lymphoma in the United States and Europe1. Patients with FL experience generally favorable outcomes with median overall survival (OS) lasting close to 18 years2. Improvements in FL survival have occurred consistently over the past several years, and for symptomatic patients treated with chemoimmunotherapy, durable disease control is achievable, lasting several years. Chemo-immunotherapy with antiCD20 antibody rituximab has changed the treatment landscape of FL by improving response rates and progression free surv...
Source: Leukemia Research - October 27, 2018 Category: Hematology Authors: Carla Casulo Source Type: research
MXD1 regulates the imatinib resistance of chronic myeloid leukemia cells by repressing BCR-ABL1 expression
Chronic myeloid leukemia (CML) is a common myeloproliferative neoplasm characterized by the chromosomal translocation t(9;22) (q34;q11) . This translocation causes the generation of a fusion oncogene, namely, the BCR-ABL1 encoding fusion protein with constitutive tyrosine kinase activity, which gives rise to the uncontrolled growth of myeloid cells in the bone marrow through a series of downstream pathways [2,3]. One of the first-line treatments for CML is imatinib, a tyrosine kinase inhibitor (TKI) that competitively binds to the ATP-binding site of Bcr-Abl and blocks the downstream signal pathway [4,5]. (Source: Leukemia Research)
Source: Leukemia Research - October 25, 2018 Category: Hematology Authors: Chen Huan, Lou Jin, Wang Heng, An Na, Pan Yuming, Du Xin, Zhang Qiaoxia Source Type: research
Intensive Chemotherapy vs. Hypomethylating Agents in Older Adults with Newly Diagnosed High-risk Acute Myeloid Leukemia: A Single Center Experience
Tremendous progress in our understanding of the biology of acute myeloid leukemia (AML) has yet to be translated into improved patient outcomes, as evidenced by a 5-yr survival rate of only 30%. This dismal outcome is driven by certain subgroups of AML patients, informally referred to as high-risk AML, characterized by advanced age, poor risk cytogenetics, and secondary AML (s-AML), therapy-related AML (t-AML), or AML with myelodysplastic related changes (AML-MRC). It is well recognized that AML patients with an adverse cytogenetic profile have worse survival than those with favorable or intermediate risk cytogenetic profi...
Source: Leukemia Research - October 25, 2018 Category: Hematology Authors: Pankit Vachhani, Raed Al Yacoub, Austin Miller, Fan Zhang, Tara L. Cronin, Evelena P. Ontiveros, James E. Thompson, Elizabeth A. Griffiths, Eunice S. Wang Tags: Research paper Source Type: research
JAK of all trades: Ruxolitinib as a new therapeutic option for CML patients
Chronic myeloid leukemia (CML) is a paradigmatic tumor in oncology research. It was the first cancer in which a recurrent chromosomal abnormality, the Philadelphia chromosome arising from the reciprocal translocation between chromosomes 9 and 22, was identified and subsequently shown to be pathogenic through the production of the fusion oncogene and tyrosine kinase (TK) BCR-ABL. CML also perfectly fits the cancer stem cell model as it arises from a leukemic stem cell (LSC) which represents the reservoir of the disease and, through self-renewal and differentiation, is able to generate the tumor bulk of mature leukemic cells...
Source: Leukemia Research - October 24, 2018 Category: Hematology Authors: Paolo Gallipoli Tags: Editorial Source Type: research
Next-generation antigen receptor sequencing of paired diagnosis and relapse samples of B-cell acute lymphoblastic leukemia: clonal evolution and implications for Minimal Residual Disease target selection
Antigen receptor (immunoglobulin (IG) and T-cell receptor (TR)) gene rearrangements can be considered as DNA fingerprints of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Consequently, they are frequently used to monitor minimal residual disease (MRD) in BCP-ALL patients . However, IG/TR gene rearrangements can be lost during the course of the disease due to outgrowth of subclones, ongoing rearrangements or secondary rearrangements, thereby resulting in false-negative MRD results [2 –8]. (Source: Leukemia Research)
Source: Leukemia Research - October 22, 2018 Category: Hematology Authors: Prisca M.J. Theunissen, Maaike de Bie, David van Zessen, V. de Haas, Andrew P. Stubbs, Vincent H.J. Van Der Velden Tags: Research paper Source Type: research
Incorporating Newer Agents in the Treatment of Acute Myeloid Leukemia
Acute myeloid leukemia (AML) represents a malignant clonal expansion of myeloid progenitor cells in the peripheral blood and bone marrow. Overall, the prognosis in AML is suboptimal, with less than 30% of AML patients achieving a long-term remission. When factoring age, as older patients are not often offered intensive therapy, survival in this group is even more morbid, and is often measured only in months.  Recently, through advancements in cytogenetic and next generation techniques, there has been a substantial improvement in the understanding of the wide genomic landscape in AML. (Source: Leukemia Research)
Source: Leukemia Research - October 19, 2018 Category: Hematology Authors: Renju V. Raj, Sameem M. Abedin, Ehab Atallah Source Type: research
CD34+ Chimerism Analysis for Minimal Residual Disease Monitoring after Allogeneic Hematopoietic Cell Transplantation
Disease relapse after allogeneic hematopoietic cell transplant (allo-HCT) remains the most common cause of mortality for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) (1). Assessment and monitoring of minimal residual disease (MRD) in these patients is often challenging because of heterogeneity of malignant clones, and the absence of well-standardized MRD assays. Chimerism analysis by the characterization of short tandem repeat (STR) markers in subpopulations of peripheral blood (PB) cells is currently widely used to monitor engraftment status and disease relapse after allo-HCT. (Source: Leukemia Research)
Source: Leukemia Research - October 17, 2018 Category: Hematology Authors: Athira Unnikrishnan, Amy M. Meacham, Steven S. Goldstein, Mai Ta, Helen L. Leather, Christopher R. Cogle, Paul Castillo, John R. Wingard, Maxim Norkin Source Type: research
The Endothelin receptor type A is a downstream target of Hoxa9 and Meis1 in Acute Myeloid Leukemia
Endothelin receptor type A (EDNRA) belongs to a G protein-coupled receptor family and is a receptor for the Endothelin-1 (ET-1) protein . ET-1 is expressed in a variety of cells, including vascular smooth muscle cells, cardiomyocytes, macrophages, leukocytes, and fibroblasts, but the main site of ET-1 production is endothelial cells . The ET-1/EDNRA axis, known as endothelin axis is involved in a diverse range of physiological and pathophysiological processes such as vasoconstriction, and cell proliferation . (Source: Leukemia Research)
Source: Leukemia Research - October 13, 2018 Category: Hematology Authors: Laleh S. Arabanian, Pegah Johansson, Anna Staffas, Tina Nilsson, Arefeh Rouhi, Linda Fogelstrand, Lars Palmqvist Tags: Research paper Source Type: research
TP53 mutation in allogeneic hematopoietic cell transplantation for de novo myelodysplastic syndrome
Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment modality available for patients with myelodysplastic syndrome (MDS). Clinical outcomes after HCT are highly variable and the selection of patients who will benefit from allogeneic HCT is essential. Allogeneic HCT is primarily recommended for higher-risk MDS patients based on findings from previous studies using Markov models that suggested the importance of appropriate timing for HCT . These statistical models showed that a decision to delay HCT would maximize survival in patients with low or intermediate-1 scores in the International Pro...
Source: Leukemia Research - October 11, 2018 Category: Hematology Authors: 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 Tags: Research paper Source Type: research
Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study
Essential thrombocythemia (ET) is the most “benign” of the myeloproliferative neoplasms (MPNs), with a near-normal expected life span [1,2]. The median age at diagnosis is approximately 60 years, but a substantial proportion of patients with ET are younger than 60 years at diagnosis. Furthermore, the life expectancy in the general popula tion has progressively improved and reached a point where individuals aged 65 years have an average life expectancy of around 20 years in developed countries. Therefore risks or side effects associated with ET treatments are especially pertinent. (Source: Leukemia Research)
Source: Leukemia Research - October 11, 2018 Category: Hematology Authors: Birgeg ård Gunnar, Folkvaljon Folke, Garmo Hans, Holmberg Lars, Besses Carlos, Griesshammer Martin, Gugliotta Luigi, Wu Jinyang, Achenbach Heinrich, Kiladjian Jean-Jacques, N. Harrison Claire Tags: Research paper Source Type: research
Immunohistochemical distinction of ABC and GCB in extranodal DLBCL is not reflected in mutation patterns
Diffuse large B cell lymphoma (DLBCL) is the most frequent form of adult lymphoma, accounting for 30-40% of diagnoses of Non Hodgkin-Lymphoma worldwide. The entity, however, is not homogenous and consists of biologically and clinically distinct subtypes. Gene expression profiling (GEP) has demonstrated at least two different types of DLBCL with distinct cells of origin. According to the gene expression patterns one type has been identified as activated B cell-like (ABC) and another as germinal center B cell-like (GCB) . (Source: Leukemia Research)
Source: Leukemia Research - October 9, 2018 Category: Hematology Authors: Cora Hallas, Michael Preukschas, Markus Tiemann Tags: Research paper Source Type: research
A phase I clinical trial of ruxolitinib in combination with nilotinib in chronic myeloid leukemia patients with molecular evidence of disease
Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome t(9;22)(q34;q11.2), which ultimately forms the BCR-ABL oncoprotein . Tyrosine kinase inhibitors (TKIs) directed against the tyrosine kinase activity of BCR-ABL are the primary therapeutic option in CML and have proven to be extremely effective at inducing hematologic, cytogenetic, and molecular remissions. Five TKIs are currently approved by health authorities for the treatment of CML: the first-generation TKI imatinib; the second-generation TKIs dasatinib, nilotinib, and bosutinib; and the third-generation TKI ponatinib [2 &n...
Source: Leukemia Research - October 8, 2018 Category: Hematology Authors: Kendra Sweet, Lori Hazlehurst, Eva Sahakian, John Powers, Lisa Nodzon, Fadi Kayali, Kelly Hyland, Ashley Nelson, Javier Pinilla-Ibarz Tags: Research paper Source Type: research
Durability of Spleen Response affects the outcome of Ruxolitinib-treated patients with myelofibrosis: results from a multicentre study on 284 patients
Ruxolitinib is the recommended medical treatment of Primary and post-Polycythemia Vera/post-Essential Thrombocythemia Myelofibrosis (PMF, PPV/PET-MF) with intermediate/high risk carrying symptomatic splenomegaly and/or MF-related symptoms . In prospective clinical trials, 60-80% of patients achieved a reduction in spleen length ≥25% during treatment [2,3]. The correlation between spleen reductions with outcome is still controversial. In a Phase 1/2 trial, patients with ≥ 50% reduction in spleen-length response (palpation) were found to have a significantly better survival, and a 5 dl increase from baseline ...
Source: Leukemia Research - October 5, 2018 Category: Hematology Authors: 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 Sg Tags: Letter to the Editor Source Type: research
NF- κB signaling activation via increases in BRD2 and BRD4 confers resistance to the bromodomain inhibitor I-BET151 in U937 cells
Bromodomain, consisting of approximately 110 amino acid residues, is a key epigenetic factor that recognizes acetylated lysine residues in histones . Proteins of the bromodomain and extra-terminal (BET) family, including bromodomain-containing protein (BRD) 2, BRD3, BRD4, and BRDT, have two tandem bromodomains and an extra-terminal domain with four alpha helices linked by two loops [1,2]. The BET family proteins play a pivotal role in the transcriptional regulation of genes through epigenetic interactions between bromodomains and acetylated histones . (Source: Leukemia Research)
Source: Leukemia Research - October 3, 2018 Category: Hematology Authors: Kotaro Hishiki, Masaharu Akiyama, Yumi Kanegae, Koji Ozaki, Miyuki Ohta, Emi Tsuchitani, Ken Kaito, Hisashi Yamada Tags: Research paper Source Type: research
RUNX1-EVI1 induces dysplastic hematopoiesis and acute leukemia of the megakaryocytic lineage in mice
The t(3;21)(q26;q22) translocation is a recurrent chromosomal abnormality found in chronic myelogenous leukemia in blastic crisis, myelodysplastic syndromes (MDS)-derived leukemia and de novo acute megakaryoblastic leukemia (AMKL) . The translocation creates the RUNX1-EVI1 fusion gene whose resultant molecules contain the N-terminus of RUNX1 and almost the entire region of EVI1 . RUNX1-EVI1 exhibits two main molecular functions . One is a dominant-negative function over normal RUNX1 function, and the other is an aberrant EVI1 expression leading to repression of TGF β signaling , inhibition of CEBPA  and...
Source: Leukemia Research - October 1, 2018 Category: Hematology Authors: Yuka Nakamura, Motoshi Ichikawa, Hideaki Oda, Ieharu Yamazaki, Ko Sasaki, Kinuko Mitani Tags: Research paper Source Type: research