Expression of the miR-150 tumor suppressor is restored by and synergizes with rapamycin in a human leukemia T-cell line
The mechanistic/mammalian target of rapamycin (mTOR) is a conserved protein kinase that induces cell growth, proliferation and changes in metabolism in response to mitogenic signals [1]. Unsurprisingly, pathogenesis and progression of numerous cancers, including T-cell acute lymphoblastic leukemia (T-ALL), is associated with constitutive activation of mTOR, caused primarily by mutations in its upstream regulators, such as AKT and PTEN [2,3]. In the majority of T-ALL patients, constitutive mTOR activation negatively affects outcomes [4]. (Source: Leukemia Research)
Source: Leukemia Research - September 22, 2018 Category: Hematology Authors: Katie Podshivalova, Eileen A. Wang, Traver Hart, Daniel R. Salomon Tags: Research paper Source Type: research
Iron overload in Myelodysplastic Syndromes: Evidence Based Guidelines from the Canadian Consortium on MDS
The myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders that lead to bone marrow failure and an increased risk of progression to acute myelogenous leukemia (AML). As many as one in 1000 Canadians over the age of 65 years may be affected [1], and data from the Surveillance, Epidemiology, and End Results (SEER) Program in the United States (US) indicates an MDS incidence up to 4.5 per 100,000 per year, or 10,000 or more new MDS diagnoses yearly [2]. The incidence of MDS increases with age, with 0.5, 5.3, 15, 49, and 89 cases per 100,000 in the age groups (Source: Leukemia Research)
Source: Leukemia Research - September 19, 2018 Category: Hematology Authors: Heather A. Leitch, Rena Buckstein, Nancy Zhu, Thomas J. Nevill, Karen W.L. Yee, Brian Leber, Mary-Margaret Keating, Eve St. Hilaire, Rajat Kumar, Robert Delage, Michelle Geddes, John M. Storring, April Shamy, Mohamed Elemary, Richard A. Wells Source Type: research
Global methylation patterns in Primary Plasma Cell Leukemia
Plasma cell leukemia (PCL) is a rare form of PC dyscrasia diagnosed by the presence of more than 20% of PCs in peripheral blood and/or an absolute PC count ≥ 2 × 109 /L [1–4]. It may occur de novo, as primary PCL (pPCL), or as secondary PCL (sPCL) from the leukemic transformation of relapsed/refractory multiple myeloma (MM) [1–4]. Main chromosomal aberrations observed in MM, with the exception of hyperdiploidy, are also identified in pPCL, a lbeit with peculiar frequencies [5–7]. Additionally, specific gene and miRNA expression profiles, and mutational patterns distinguish pPCL from MM [5,8–10]. (Source: Leukemia Research)
Source: Leukemia Research - September 18, 2018 Category: Hematology Authors: Katia Todoerti, Giovanni Calice, Stefania Trino, Vittorio Simeon, Marta Lionetti, Martina Manzoni, Sonia Fabris, Marzia Barbieri, Alessandra Pompa, Luca Baldini, Valentina Bollati, Pietro Zoppoli, Antonino Neri, Pellegrino Musto Tags: Research paper Source Type: research
Clustered Incidence of Adult Acute Promyelocytic Leukemia
Acute promyelocytic leukemia (APL) is characterized by the presence of a translocation between chromosomes 15 and 17 resulting in the PML-RARA fusion. In 2011, we noted an increase in APL cases at our institution. We surveyed six major hospitals in the greater Boston area and Massachusetts Cancer Registry to identify incident APL cases, and describe the demographic and clinical characteristics of these patients between 2004 and 2014. We identified multiple peaks in incident cases and explore geographic and temporal trends that merit further investigation to determine whether environmental exposures may contribute to leukem...
Source: Leukemia Research - September 18, 2018 Category: Hematology Authors: Andrew M. Brunner, Peter G. Kim, Hossein Sadrzadeh, Benjamin J. Drapkin, Kellie A. Sprague, J. Mark Sloan, Wanxing Chai-Ho, Parul Bhargava, Olga Pozdnyakova, Amir T. Fathi Tags: Letter to the Editor Source Type: research
Genomic Aberrations Involving 12p/ETV6 Are Highly Prevalent in Blastic Plasmacytoid Dendritic Cell Neoplasms and Might Represent Early Clonal Events
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic neoplasm derived from plasmacytoid dendritic cells. Skin lesions are the most common presenting clinical feature, seen in nearly 85% of patients. While some patients may present with disease localized to the skin, most present with or eventually develop systemic involvement most commonly involving the bone marrow.[1 –3] Patients have a median survival of 12 months, and to date therapeutic options remain limited in scope and effectiveness, with the only curative option being stem cell transplant (SCT) therapy in eligible patients.[4] Most pa...
Source: Leukemia Research - September 17, 2018 Category: Hematology Authors: Zhenya Tang, Yan Li, Wei Wang, C. Cameron Yin, Guilin Tang, Phyu P. Aung, Shimin Hu, Xinyan Lu, Gokce A Toruner, L. Jeffrey Medeiros, Joseph D. Khoury Tags: Research paper Source Type: research
Pharmacogenomics and variations in the risk of toxicity during the consolidation/maintenance phases of the treatment of pediatric b-cell leukemia patients from an admixed population in the brazilian amazon
Acute Lymphoblastic Leukemia (ALL) is the most common childhood cancer, representing approximately 30% of all malignant pediatric neoplasia [1,2]. In about 85% of children with ALL, the leukemia starts in the B cells (B-cell ALL). Recent advances in the chemotherapy of childhood ALL, based on a cocktail of chemotherapeutic drugs that includes inhibitors of tyrosine kinases, have resulted in survival rates of>90% [3]. Despite the clinical success of this treatment, around 20% of the children present serious toxicological complications that require a reduction in the dosage or even the complete interruption of the treatment ...
Source: Leukemia Research - September 15, 2018 Category: Hematology Authors: Darlen Cardoso de Carvalho, Alayde Vieira Wanderley, Andr é Mauricio Ribeiro dos Santos, Marianne Rodrigues Fernandes, Amanda de Nazaré Cohen Lima de Castro, Luciana Pereira Colares Leitão, João Augusto Nunes de Carvalho Junior, Tatiane Piedade de Sou Source Type: research
Phase I study of ruxolitinib in previously treated patients with low or intermediate-1 risk myelodysplastic syndrome with evidence of NF-kB activation
Myelodysplastic syndromes (MDS) are a diverse group of clonal myeloid disorders characterized by ineffective hematopoiesis, cytopenias, and a tendency towards transformation to acute myeloid leukemia (AML) [1]. Based on the International Prognostic Scoring System (IPSS), patients with MDS are prognostically stratified into either lower-risk (low and intermediate-1) or higher-risk (intermediate-2 and high) disease [2]. By the revised IPSS, lower-risk includes very low, low, and a fraction of intermediate-risk patients [3,4]. (Source: Leukemia Research)
Source: Leukemia Research - September 14, 2018 Category: Hematology Authors: Yasmin Abaza, Juliana E. Hidalgo-Lopez, Srdan Verstovsek, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Zeev Estrov, Yesid Alvarado, Jan Burger, Heather Schneider, Kelly A. Soltysiak, Yue Wei, Hagop M. Kantarjian, Carlos E. Bueso-Ramos, Guillermo Garci Tags: Research paper Source Type: research
Challenging "privileged" stereotypes – Leukemic blasts and the central nervous system
The successful cure of over 90% of children with acute lymphoblastic leukaemia (ALL) is one of the most impressive achievements of the last 50 years in haematology. However, challenges remain. One particularly problematic area is how best to prevent and/or treat leukaemic relapse in the central nervous system (CNS). Early studies established that CNS-directed therapy is essential for cure. Accordingly, all modern ALL treatment protocols include large amounts of CNS-directed chemotherapy irrespective of the presence or absence of detectable CNS disease at presentation. (Source: Leukemia Research)
Source: Leukemia Research - September 11, 2018 Category: Hematology Authors: Christina Halsey Tags: Commentary Source Type: research
Challenging "privileged" stereotypes - leukemic blasts and the central nervous system
The successful cure of over 90% of children with acute lymphoblastic leukaemia (ALL) is one of the most impressive achievements of the last 50 years in haematology. However, challenges remain. One particularly problematic area is how best to prevent and/or treat leukaemic relapse in the central nervous system (CNS). Early studies established that CNS-directed therapy is essential for cure. Accordingly, all modern ALL treatment protocols include large amounts of CNS-directed chemotherapy irrespective of the presence or absence of detectable CNS disease at presentation. (Source: Leukemia Research)
Source: Leukemia Research - September 11, 2018 Category: Hematology Authors: Christina Halsey Tags: Commentary Source Type: research
Over 20 years of treatment-free remission after Interferon-alpha monotherapy for Chronic Myeloid Leukemia
Chronic myeloid leukemia (CML) is a clonal malignancy characterized by the acquisition of the chromosomal translocation t(9;22), also termed Philadelphia chromosome [1], resulting in the formation of the BCR-ABL1 fusion protein. Historically, patients treated with chemotherapy such as busulfan or hydroxyurea had a grim prognosis with a median overall survival (OS) of only 4 years [2]. (Source: Leukemia Research)
Source: Leukemia Research - September 11, 2018 Category: Hematology Authors: Jonathan Bloch, Olivier Spertini, Anne Stucki, Francoise Solly, Sabine Blum Tags: Letter to the Editor Source Type: research
Recently approved therapies in acute myeloid leukemia: a complex treatment landscape
Acute myeloid leukemia (AML) is a heterogeneous disease with multiple molecular pathways driving its progression [1,2]. It is a clonal hematopoietic disorder characterized by uncontrolled proliferation without differentiation of myeloid progenitors [3]. With an approximate 5-year survival rate of 27%, AML has a particularly poor prognosis and is rapidly fatal if left untreated [4]. (Source: Leukemia Research)
Source: Leukemia Research - September 8, 2018 Category: Hematology Authors: Chetasi Talati, Kendra Sweet Source Type: research
Differing clinical features between Japanese and Caucasian patients with myelodysplastic syndromes: Analysis from the International Working Group for Prognosis of MDS
Patients with myelodysplastic syndromes (MDS) show heterogeneous clinical features with variation in ineffective hematopoiesis, morphological dysplasia, and progression to acute myeloid leukemia (AML) [1]. MDS arises from abnormal hematopoietic stem cells, with detectable somatic mutations in virtually all patients [2,3], and recent studies also showed that germline mutations are found in a portion of MDS [4,5]. These results clearly demonstrate that the genomic status is highly influential on clinical features of MDS [3]. (Source: Leukemia Research)
Source: Leukemia Research - September 6, 2018 Category: Hematology Authors: Yasushi Miyazaki, Heinz Tuechler, Guillermo Sanz, Julie Schanz, Guillermo Garcia-Manero, Francesc Sol é, John M. Bennett, David Bowen, Pierre Fenaux, Francois Dreyfus, Hagop Kantarjian, Andrea Kuendgen, Luca Malcovati, Mario Cazzola, Jaroslav Cermak, Chr Tags: Research paper Source Type: research
Canadian chronic myeloid leukemia outcomes post-transplant in the tyrosine kinase inhibitor era
Allogeneic hematopoietic stem cell transplantation (HCT) remains a potentially curative option for CML patients who have failed multiple tyrosine kinase inhibitors (TKI ’s) or progressed to advanced disease. In patients with TKI failure, the majority (89%) responded to HCT with 68% achieving at least a major molecular response (MMR) [1]. Disease phase, found to be a major prognostic factor affecting transplant outcomes in the pre-TKI era, remains significant in t he TKI era. The 3-year survival rate has been reported as 91% in chronic phase (CP) vs 59% in advanced disease phase patients transplanted in the TKI-era [2]. (...
Source: Leukemia Research - September 5, 2018 Category: Hematology Authors: Mary Lynn Savoie, Isabelle Bence-Bruckler, Lothar B. Huebsch, Marc Lalancette, Chris Hillis, Irwin Walker, Jeffrey H. Lipton, Donna L. Forrest, Dennis (Dong Hwan) Kim Tags: Research paper Source Type: research
Association between health literacy, communication and psychological distress among myelodysplastic syndromes patients
A diagnosis of myelodysplastic syndrome (MDS), i.e. a cancerous disease with a variable risk of evolution into acute myeloid leukaemia [1] can trigger different emotions, particularly, psychological distress [2], as MDS can potentially be a life-threatening disease without any curative treatment except stem-cell transplant, which is not applicable for most patients [3]. Among lower-risk patients watchful waiting or symptomatic treatment might also generate distress because of the lack of MDS-focused treatment. (Source: Leukemia Research)
Source: Leukemia Research - September 4, 2018 Category: Hematology Authors: Youssoufa M. Ousseine, Phyllis N. Butow, Pierre Fenaux, Rebecca Dring, Patrick Festy, L éa Restivo, Norbert Vey, Julien Mancini Source Type: research
Granular B-Acute Lymphoblastic Leukemia: Ultrastructural Characterization of Cytoplasmic Granules
The presence of cytoplasmic granules in the blasts is a well-known feature of acute leukemia with myeloid differentiation, whereas cases of B-acute lymphoblastic leukemia (B-ALL) with cytoplasmic granules in blasts are rare and potentially may be misdiagnosed as acute myeloid leukemia. Cases of B-ALL with cytoplasmic granules have been described most often in pediatric patients and others have proposed a criterion for granular ALL being more than 5% of lymphoblasts having three or more clearly defined azurophilic granules [1]. (Source: Leukemia Research)
Source: Leukemia Research - September 1, 2018 Category: Hematology Authors: Huanling Wu, Bing Liu, Boqin Li, Yong Wang, Haibo Wang, L. Jeffrey Medeiros, Bingchang Zhang, Wei Wang Tags: Letter to the Editor Source Type: research
