Modeling myeloproliferative neoplasms: From mutations to mouse models and back again
Myeloproliferative neoplasms (MPNs) are defined according to the 2008 World Health Organization (WHO) classification and the recent 2016 revision. Over the years, several genetic lesions have been associated with the development of MPNs, with important consequences for identifying unique biomarkers associated with specific neoplasms and for developing targeted therapies. Defining the genotype-phenotype relationship in MPNs is essential to identify driver somatic mutations that promote MPN development and maintenance in order to develop curative targeted therapies. (Source: Blood Reviews)
Source: Blood Reviews - November 22, 2016 Category: Hematology Authors: Alessandro Morotti, Stefania Rocca, Giovanna Carr à, Giuseppe Saglio, Mara Brancaccio Tags: Review Source Type: research
Therapy-related myelodysplastic syndromes, or are they?
The incidence of therapy-related myelodysplastic syndromes (t-MDS) is increasing as the number of cancer survivors is increasing. While t-MDS is currently defined descriptively by prior receipt of chemotherapy and/or radiotherapy, some forms of MDS that occur post localized radiation monotherapy, biologically and clinically resemble de novo (d)-MDS more than t-MDS, and therefore may not be truly therapy-related. Although patients with t-MDS, as a group, fare worse than patients with d-MDS, a variation in individual outcomes of patients with t-MDS has increasingly been appreciated. (Source: Blood Reviews)
Source: Blood Reviews - November 22, 2016 Category: Hematology Authors: Abdallah Abou Zahr, Ami M. Kavi, Sudipto Mukherjee, Amer M Zeidan Tags: Review Source Type: research
MicroRNA: Defining a new niche in Leukemia
MicroRNAs (miRNAs) are endogenous short non-coding RNAs found to play key roles in the pathogenesis of leukemia. Apart from being traditionally identified as modulators of oncogenes, the potential roles of miRNAs seems to be growing with novel and recent findings among different subtypes of hematological malignancies.Leukemia is one of the earliest malignancies to be linked to abnormal expression of miRNAs. However, a clear understanding of the involvement of miRNAs in intricate mechanisms of leukemogenesis is still a necessity. (Source: Blood Reviews)
Source: Blood Reviews - November 22, 2016 Category: Hematology Authors: Queenie Fernandes Tags: Review Source Type: research
After 10years of JAK2V617F: Disease biology and current management strategies in polycythaemia vera
The JAK2V617F mutation accounts for the vast majority of patients with polycythaemia vera (PV) and around half of those with other Philadelphia-negative myeloproliferative neoplasms. Since its discovery in 2005, numerous insights have been gained into the pathways by which JAK2V617F causes myeloproliferation, including activation of JAK-STAT signalling but also through other canonical and non-canonical pathways. A variety of mechanisms explain how this one mutation can be associated with distinct clinical disorders, demonstrating how constitutional and acquired factors may interact in the presence of a single mutation to d...
Source: Blood Reviews - November 14, 2016 Category: Hematology Authors: Jacob Grinfeld, Anna L Godfrey Tags: Review Source Type: research
NF- κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms
The NF- κB pathway, a critical regulator of apoptosis, plays a key role in many normal cellular functions. Genetic alterations and other mechanisms leading to constitutive activation of the NF-κB pathway contribute to cancer development, progression and therapy resistance by activation of downstream anti- apoptotic pathways, unfavorable microenvironment interactions, and gene dysregulation. Not surprisingly, given its importance to normal and cancer cell function, the NF-κB pathway has emerged as a target for therapy. (Source: Blood Reviews)
Source: Blood Reviews - October 12, 2016 Category: Hematology Authors: Li Yu, Ling Li, L. Jeffrey Medeiros, Ken H. Young Tags: Review Source Type: research
Recent discoveries in the molecular pathogenesis of the inherited bone marrow failure syndrome Fanconi anemia
Fanconi anemia (FA) is a rare autosomal and X-linked genetic disease characterized by congenital abnormalities, progressive bone marrow failure (BMF), and increased cancer risk during early adulthood. The median lifespan for FA patients is approximately 33years. The proteins encoded by the FA genes function together in the FA-BRCA pathway to repair DNA damage and to maintain genome stability. Within the past two years, five new FA genes have been identified - RAD51/FANCR, BRCA1/FANCS, UBE2T/FANCT, XRCC2/FANCU, and REV7/FANCV - bringing the total number of disease-causing genes to 21. (Source: Blood Reviews)
Source: Blood Reviews - October 12, 2016 Category: Hematology Authors: Nicholas E. Mamrak, Akiko Shimamura, Niall G. Howlett Tags: Review Source Type: research
Selecting initial treatment of acute myeloid leukaemia in older adults
More than half of the patients with acute myeloid leukaemia (AML) are older than 60years. The treatment outcomes in this group remain poor with a median overall survival of (Source: Blood Reviews)
Source: Blood Reviews - October 6, 2016 Category: Hematology Authors: Nikolai A. Podoltsev, Maximilian Stahl, Amer M. Zeidan, Steven D. Gore Tags: Review Source Type: research
Monitoring Minimal Residual Disease in Acute Leukemia: Technical Challenges and Interpretive Complexities
Minimal residual disease (MRD) after therapy has unequivocal prognostic value in acute leukemia. Over the past 20years, a number of techniques have evolved into routine laboratory tools to detect MRD, most notably, multiparametric flow cytometry (MFC) and quantitative polymerase chain reaction (PCR)-based molecular methods. There is growing evidence that the presence of MRD detected by MFC or molecular methods provides independent prognostic information and is associated with an increased risk of relapse and shortened survival. (Source: Blood Reviews)
Source: Blood Reviews - October 4, 2016 Category: Hematology Authors: Xueyan Chen, Brent L. Wood Tags: Review Source Type: research
High Grade B-Cell Lymphoma with Rearrangements of MYC and BCL2 and/or BCL6: Double Hit and Triple Hit Lymphomas and Double Expressing Lymphoma
Conclusions to date have largely been drawn from retrospective data although prospective data is slowly starting to emerge. Chemoimmunotherapy refractoriness is problematic and relapse rates are high. (Source: Blood Reviews)
Source: Blood Reviews - September 29, 2016 Category: Hematology Authors: Allison Rosenthal, Anas Younes Tags: REVIEW Source Type: research
Use of clinical prediction rules and D-dimer tests in the diagnostic management of pregnant patients with suspected acute pulmonary embolism
Because pregnant women have an increased risk of venous thromboembolism (VTE) and at the same time normal pregnancy is associated with symptoms, mimicking those present in the setting of acute pulmonary embolism (PE), the latter diagnosis is frequently suspected in this patient category. Since imaging tests expose both mother and foetus to ionizing radiation, the ability to rule out PE based on non-radiological diagnostic tests is of paramount importance. However, clinical decision rules have only been scarcely evaluated in the pregnant population with suspected PE, while D-dimer levels lose diagnostic accuracy due to a ph...
Source: Blood Reviews - September 28, 2016 Category: Hematology Authors: LM Van der Pol, ATA Mairuhu, C Tromeur, F Couturaud, MV Huisman, FA Klok Tags: Review Source Type: research
BCR-ABL (Ph)-like acute leukemia —Pathogenesis, diagnosis and therapeutic options
Recent comprehensive genetic studies revealed numerous genetic aberrations underlying a group of high-risk leukemias that share a specific activated kinase gene expression pattern. These ALLs were first recognized by the expression profile similar to that of Philadelphia chromosome-positive ALL and currently can be sub-classified by the main aberrantly activated kinase in the leukemic cells. We herein review the biological mechanisms and diagnostic and clinical challenges presented by these leukemias. (Source: Blood Reviews)
Source: Blood Reviews - September 15, 2016 Category: Hematology Authors: Yishai Ofran, Shai Izraeli Tags: REVIEW Source Type: research
BCR-ABL (Ph)-like acute leukemia – pathogenesis, diagnosis and therapeutic options
Recent comprehensive genetic studies revealed numerous genetic aberrations underlying a group of high-risk leukemias that share a specific activated kinase gene expression pattern. These ALLs were first recognized by the expression profile similar to that of Philadelphia chromosome positive ALL and currently can be sub-classified by the main aberrantly activated kinase in the leukemic cells. We herein review the biological mechanisms and diagnostic and clinical challenges presented by these leukemias. (Source: Blood Reviews)
Source: Blood Reviews - September 15, 2016 Category: Hematology Authors: Yishai Ofran, Shai Izraeli Tags: REVIEW Source Type: research
Risk Stratification for Invasive Fungal Infections in Patients with Hematological Malignancies: SEIFEM recommendations
Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in immunocompromised patients. Patients with hematological malignancies undergoing conventional chemotherapy, autologous or allogeneic hematopoietic stem cell transplantation are considered at high risk, and Aspergillus spp. represents the most frequently isolated micro-organisms. In the last years, attention has also been focused on other rare molds (e.g., Zygomycetes, Fusarium spp.) responsible for devastating clinical manifestations. (Source: Blood Reviews)
Source: Blood Reviews - September 15, 2016 Category: Hematology Authors: Livio Pagano, Alessandro Busca, Anna Candoni, Chiara Cattaneo, Simone Cesaro, Rosa Fanci, Gianpaolo Nadali, Leonardo Potenza, Domenico Russo, Mario Tumbarello, Annamaria Nosari, Franco Aversa, on behalf of SEIFEM (Sorveglianza Epidemiologica Infezioni Fun Tags: REVIEW Source Type: research
Natural Killer Cells in Malignant Hematology: A Primer for the Non-Immunologist
Natural killer cells were first described over 40years ago, but the last 15years has shown tremendous progress in our understanding of their biology and our ability to manipulate them for clinical therapeutic effect. Despite the increased understanding by clinicians and scientists investigating these cells, their biology remains a confusing subject for many because of the wide array of receptors, complex interactions, multiple models of predicting function, and contradictory data in the literature. (Source: Blood Reviews)
Source: Blood Reviews - September 7, 2016 Category: Hematology Authors: Geoffrey S. Kannan, Arianexys Aquino-Lopez, Dean A. Lee Tags: Review Source Type: research
Molecular Biomarkers in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The pathophysiology of this disease is just beginning to be understood at the cellular and molecular level, and currently cytogenetic markers are the most important for risk stratification and treatment of AML patients. However, with the advent of new technologies, the detection of other molecular markers such as point mutations and characterization of epigenetic and proteomic profiles, have begun to play an important role in how the disease is approached. (Source: Blood Reviews)
Source: Blood Reviews - September 1, 2016 Category: Hematology Authors: Jeanette Prada-Arismendy, Johanna Arroyave Ospina, Sarah R öthlisberger Tags: REVIEW Source Type: research
