Keeping the kraken asleep: Insight into the role of stem cells in leukemia

Despite enormous progress in cancer therapy, many patients still relapse because their treatment addresses the symptoms of the disease rather than the cause, the so-called stem cells. New work has given a tantalizing clue to a solution. Scientists report that the cell-cycle kinase CDK6 is required for activation of the stem cells responsible for causing leukemia.
Source: ScienceDaily Headlines - Category: Science Source Type: news

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For years, cancer treatment was dominated by chemotherapy, radiation therapy, and stem cell transplantation. New insights into genetic characteristics of leukemic cells have initiated the development of the chimeric antigen receptor (CAR) T-cell therapy. This type of adoptive cell immunotherapy has been a breakthrough in the treatment of aggressive B-cell lymphoma and B-cell precursor acute lymphoblastic leukemia. In August 2018, the European Commission has approved the first CAR T-cell products – tisagenlecleucel (Kymriah®, Novartis) and axicabtagene ciloleucel (Yescarta®, Gilead) – for hematological n...
Source: Transfusion Medicine and Hemotherapy - Category: Hematology Source Type: research
to AP Abstract Cancer stem cells show epigenetic plasticity and intrinsic resistance to anti-cancer therapy, rendering capable of initiating cancer relapse and progression. Transcription factor OCT-4 regulates various pathways in stem cells, but its expression can be regulated by pseudogenes. This work evaluated how OCT4-PG1 pseudogene can affect OCT-4 expression and mechanisms related to the multidrug resistance (MDR) phenotype in FEPS cells. Considering that OCT-4 protein is a transcription factor that regulates expression of ABC transporters, level of gene expression, activity of ABC proteins and cell sensitivi...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
In this study, we show that calorie restriction is protective against age-related increases in senescence and microglia activation and pro-inflammatory cytokine expression in an animal model of aging. Further, these protective effects mitigated age-related decline in neuroblast and neuronal production, and enhanced olfactory memory performance, a behavioral index of neurogenesis in the SVZ. Our results support the concept that calorie restriction might be an effective anti-aging intervention in the context of healthy brain aging. Greater Modest Activity in Late Life Correlates with Lower Incidence of Dementia ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Adults diagnosed with acute myeloid leukemia have a poor prognosis, with only 30% surviving at five years. Despite advances in our understanding of the molecular underpinnings of AML, the chemotherapy backbone used to treat most patients (combination cytarabine and anthracycline) remains unchanged since 1973.With the goal of identifying a new differentiation therapy, we previously performed a small molecule phenotypic screen to find compounds that triggered myeloid maturation. Unexpectedly, our most active hits were inhibitors of the enzyme dihydroorotate dehydrogenase (DHODH). The DHODH-inhibitor brequinar demonstrated dr...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II Source Type: research
This study investigated the effects of PTL and SSZ on unsorted, CD200+ and CD200- BCP-ALL subpopulations in the presence of MSC. Six MRD low risk and 4 risk cases were co-cultured on MSC, at a 2:1 ratio, 1 hour prior to addition of PTL at various doses up to 10mM. After 24 hours, cells were stained with Annexin V and PI and viability was assessed by flow cytometry. In the absence of MSC, low risk cases were slightly less sensitive to PTL with an IC50 of 2.23mM compared to risk ones (IC50 1.54mM, P=0.61). Interestingly, 4 of 6 low risk cases, which were less sensitive to PTL, had normal karyotypes, while the 2 responsive ca...
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster III Source Type: research
The hematopoietic system is one of the most well-studied and well-characterized differentiation hierarchies in the mammalian body, and hematopoiesis has for decades served as a paradigm for how stem cells generate complex, self-renewing tissues and maintain them under homeostatic, physiological stress and regenerative conditions. The hematopoietic stem cell (HSC) plays a central role in all of these scenarios: HSCs provide the developmental origin of definitive hematopoiesis, sustain baseline blood cell production and are activated in response to physiological stress. In addition, HSC are capable of regenerating the hemato...
Source: Blood - Category: Hematology Authors: Tags: Thrombopoiesis Revised: From Lung to Hematopoietic Stem Cell Platelet Bias Source Type: research
The objective of this study was to explore whether changes in serum markers of inflammation underlie differences in cognitive functioning among patients treated for hematological malignancies.Methods. The sample comprised participants treated for lymphoma or multiple myeloma who were participating in a feasibility study of a computerized cognitive training program. Prior to the intervention, a battery of neuropsychological tests were administered to assess cognitive function in the following domains: Learning Efficiency and Memory; Information Processing and Psychomotor Efficiency; and Executive Functioning and Working Mem...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions Source Type: research
Conclusions: This study demonstrated the efficacy and safety of the recommended dose level of blinatumomab in a high-risk adult R/R ALL population. Response rates in Japanese patients were consistent with those in global studies, and no new safety signals were identified.DisclosuresKobayashi: Ohtuka: Research Funding; Pfizer: Research Funding; Astellas: Research Funding. Zimmerman: Amgen Inc.: Employment, Equity Ownership. Minami: Kyowa-Kirin: Honoraria, Research Funding; MSD: Honoraria, Other: Clinical Trial, Research Funding; Ono Yakuhin: Honoraria, Other: Clinical Trial, Research Funding; Behringer: Honoraria, Research ...
Source: Blood - Category: Hematology Authors: Tags: 612. Acute Lymphoblastic Leukemia: Clinical Studies Source Type: research
Conclusions: The most common regimen during LOT1 was bendamustine + rituximab, and was ibrutinib during LOT2 and LOT3.This study provides evidence that occurrence of AEs among patients with CLL receiving systemic anti-cancer therapy in the real-world setting is substantial and associated with significant health care cost. The economic burden associated with increased AEs underscores the need for treatments with fewer AEs.Figure.DisclosuresKabadi: AstraZeneca: Employment. Le: Optum: Employment; Optum/United Health Group: Equity Ownership. Dacosta Byfield: Optum/United Health Group: Equity Ownership; Optum: Employment. Olufa...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Real World Outcomes Source Type: research
(UCLA Samueli School of Engineering) A cancer therapy based on fusing two types of cells into a single unit shows promise in strengthening existing treatments for acute myeloid leukemia. The approach joins blood platelets that carry cancer drugs with stem cells that guide the platelets into bone marrow where leukemia begins.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
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