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 [1]. 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. [1] 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 [1]. 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 [2]. 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 [3]. (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 [1]. 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) [1]. (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 [1]. 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 ...
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 [1]. 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 in sple...
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 [1]. 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 [2]. (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) [1]. The translocation creates the RUNX1-EVI1 fusion gene whose resultant molecules contain the N-terminus of RUNX1 and almost the entire region of EVI1 [2]. RUNX1-EVI1 exhibits two main molecular functions [3]. 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 [4], inhibition of CEBPA [5] and sti...
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
Welcome Address
(Source: Leukemia Research)
Source: Leukemia Research - October 1, 2018 Category: Hematology Source Type: research
Hematology Specialist Association
(Source: Leukemia Research)
Source: Leukemia Research - October 1, 2018 Category: Hematology Source Type: research
