New way to halt leukemia relapse shown promising in mice

(Hiroshima University) Drugs tackling chronic myelogenous leukemia have completely transformed prognoses of patients over the last couple of decades, with most cases going into remission. But drug resistance can occur, leading to relapses. Targeting the lipids involved in regulating part of a leukemia stem cell's life span offers a potential second route to defeat the disease--and solid tumorous cancers as well.
Source: EurekAlert! - Biology - Category: Biology Source Type: news

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Chronic myeloid leukemia (CML) results from a translocation between chromosomes 9 and 22, which generates the Philadelphia chromosome. This forms BCR/ABL1, an active tyrosine kinase protein that promotes cell growth and replication. Despite great progress in CML treatment in the form of tyrosine kinase inhibitors, allogeneic-hematopoietic stem cell transplantation (allo-HSCT) is currently used as an important treatment alternative for patients resistant to these inhibitors. Studies have shown that unregulated expression of microRNAs, which act as oncogenes or tumor suppressors, is associated with human cancers. This contri...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Hun Sik Kim The BCR-ABL1 fusion gene generating an oncogenic tyrosine kinase is a hallmark of chronic myeloid leukemia (CML), which can be successfully targeted by BCR-ABL1 tyrosine kinase inhibitors (TKIs). However, treatment-free remission has been achieved in a minority of patients due to evolving TKI resistance and intolerance. Primary or acquired resistance to the approved TKIs and progression to blast crisis (BC), thus, remain a major clinical challenge that requires alternative therapeutic strategies. Here, we first demonstrate that donor natural killer (NK) cells prepared using a protocol adopted in clinical tr...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Brief Report Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Patients with chronic myeloid leukemia (CML) often require lifelong therapy with ABL1 tyrosine kinase inhibitors (TKIs) due to a persisting TKI-resistant population of leukemic stem cells (LSCs). From transcriptome profiling, we show integrin-linked kinase (ILK), a key constituent of focal adhesions, is highly expressed in TKI-nonresponsive patient cells and their LSCs. Genetic and pharmacological inhibition of ILK impaired the survival of nonresponder patient cells, sensitizing them to TKIs, even in the presence of protective niche cells. Furthermore, ILK inhibition eliminated TKI-refractory LSCs from pa...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
Contributor : Roman SasikSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWhile Chronic Myelogenous Leukemia (CML) is generally well controlled with Imatinib and other kinase inhibitors, blast crisis CML (bcCML) continues to be resistant to current therapies and remains highly lethal. Here we report a genome-wide in vivo CRISPR screen to better define the biological determinants of bcCML establishment and propagation in a physiologic context. This screen identified a large number of new genes and programs critically required for bcCML including those essential for chromatin remodeling,...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Abstract New strategies to eradicate cancer stem cells in chronic myeloid leukemia (CML) include a combination of imatinib with peroxisome proliferator-activated receptor gamma (PPARγ) ligands. Recently, we identified the partial PPARγ agonist telmisartan as effective sensitizer of resistant K562 CML cells to imatinib treatment. Here, the importance of the heterocyclic core  on the cell death modulating effects  of the telmisartan-derived lead  4'-((2-propyl-1 H -benzo[ d ]imidazol-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid was investigated. Inspired by the  pharmacodynamics of ...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative neoplasm resulting from BCR –ABL-transformed hematopoietic stem cells. Previous research has implicated multifunctional proinflammatory cytokine...
Source: Cancer Cell International - Category: Cancer & Oncology Authors: Tags: Primary research Source Type: research
Cancers, Vol. 12, Pages 318: HDAC6—an Emerging Target Against Chronic Myeloid Leukemia? Cancers doi: 10.3390/cancers12020318 Authors: Hélène Losson Michael Schnekenburger Mario Dicato Marc Diederich Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Several studies have highlighted the role of histon...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
tsch JJ Abstract Chronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR-ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR-ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1-mediated pathways and related factors that may help to further eradicate minimal residual di...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
The anti-leukemia activity of NK cells helps prevent relapse during hematopoietic stem cell transplantation (HSCT) in leukemia patients. However, the factors that determine the sensitivity or resistance of leukemia cells in the context of NK-mediated cytotoxicity are not well-established. Here, we performed a genome-wide CRISPR screen in the human chronic-myelogenous-leukemia (CML) cell line K562 to identify genes that regulate the vulnerability of leukemia cells to killing by primary human NK cells. The distribution of guide RNAs (gRNAs) in K562 cells that survived co-incubation with NK cells showed that loss of NCR3LG1, ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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