25,874 results match your criteria Chronic Myelogenous Leukemia

Successful Preservation of Native BCR::ABL1 in Chronic Myeloid Leukemia Primary Leukocytes Reveals a Reduced Kinase Activity.

Front Oncol 2022 8;12:904510. Epub 2022 Jun 8.

Department of Medicine, General Pathology Section, University of Verona, Verona, Italy.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the acquisition of t(9;22) generating the fusion tyrosine kinase BCR::ABL1. However, despite the crucial role of this protein in the dysregulation of numerous signal transduction pathways, a direct measure of BCR::ABL1 kinase activity in chronic phase (CP) CML was never accomplished due to intense degradative activity present in mature leukocytes. Therefore, we developed a procedure suitable to preserve BCR::ABL1 protein under non-denaturing, neutral pH conditions in primary, chronic phase (CP)-CML samples. Read More

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c-Abl controls BCR signaling and B cell differentiation by promoting B cell metabolism.

Immunology 2022 Jun 26. Epub 2022 Jun 26.

Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

As a non-receptor tyrosine kinase, c-Abl was first studied in chronic myelogenous leukemia, and its role in lymphocytes has been well characterized. c-Abl is involved in B cell development and CD19 associated B cell antigen receptor (BCR) signaling. Although c-Abl regulates different metabolic pathways, the role of c-Abl is still unknown in B cell metabolism. Read More

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CRISPR/Cas9-Directed Gene Trap Constitutes a Selection System for Corrected Leukemic Cells in CML.

Int J Mol Sci 2022 Jun 7;23(12). Epub 2022 Jun 7.

Departamento de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain.

Chronic myeloid leukaemia (CML) is a haematological neoplasm driven by the fusion oncogene. The monogenic aspect of the disease and the feasibility of ex vivo therapies in haematological disorders make CML an excellent candidate for gene therapy strategies. The ability to abolish any coding sequence by CRISPR-Cas9 nucleases offers a powerful therapeutic opportunity to CML patients. Read More

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The Impact of SKP2 Gene Expression in Chronic Myeloid Leukemia.

Genes (Basel) 2022 May 26;13(6). Epub 2022 May 26.

Clinical Pathology Department, Tanta University, Tanta 31527, Egypt.

Introduction: The prognosis of chronic myeloid leukemia (CML) patients has been dramatically improved with the introduction of imatinib (IM), the first tyrosine kinase inhibitor (TKI). TKI resistance is a serious problem in IM-based therapy. The human S-phase kinase-associated protein 2 () gene may play an essential role in the genesis and progression of CML. Read More

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Coiled-coil heterodimer-based recruitment of an exonuclease to CRISPR/Cas for enhanced gene editing.

Nat Commun 2022 Jun 23;13(1):3604. Epub 2022 Jun 23.

Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, Ljubljana, 1000, Slovenia.

The CRISPR/Cas system has emerged as a powerful and versatile genome engineering tool, revolutionizing biological and biomedical sciences, where an improvement of efficiency could have a strong impact. Here we present a strategy to enhance gene editing based on the concerted action of Cas9 and an exonuclease. Non-covalent recruitment of exonuclease to Cas9/gRNA complex via genetically encoded coiled-coil based domains, termed CCExo, recruited the exonuclease to the cleavage site and robustly increased gene knock-out due to progressive DNA strand recession at the cleavage site, causing decreased re-ligation of the nonedited DNA. Read More

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Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells.

Oncol Rep 2022 Aug 22;48(2). Epub 2022 Jun 22.

Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig‑Holstein, Campus Kiel, D-24105 Kiel, Germany.

Although chronic myeloid leukemia (CML) can be effectively treated using BCR‑ABL1 kinase inhibitors, resistance due to kinase alterations or to BCR‑ABL1 independent mechanisms remain a therapeutic challenge. For the latter, the underlying mechanisms are widely discussed; for instance, gene expression changes, epigenetic factors and alternative signaling pathway activation. In the present study, ‑CML cell models of resistance against the tyrosine kinase inhibitors (TKIs) imatinib (0. Read More

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Detachment of Hexokinase II From Mitochondria Promotes Collateral Sensitivity in Multidrug Resistant Chronic Myeloid Leukemia Cells.

Front Oncol 2022 26;12:852985. Epub 2022 May 26.

Laboratório de Trombose e Câncer, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Chronic Myeloid Leukemia is a neoplastic disease characterized by the abnormal expansion of hematopoietic cells with compromised functions. Leukemic cells often display a multidrug resistance phenotype, enabling them to evade a number of structurally unrelated cytotoxic compounds. One of those mechanisms relies on the high expression of efflux transporters, such as the ABC proteins, whose activity depends on the hydrolysis of ATP to reduce intracellular drug accumulation. Read More

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Targeting UPR signaling pathway by dasatinib as a promising therapeutic approach in chronic myeloid leukemia.

Med Oncol 2022 Jun 18;39(9):126. Epub 2022 Jun 18.

Department of Medical Biology, Faculty of Medicine, Ege University, Bornova, 35100, Izmir, Turkey.

Chronic myeloid leukemia (CML) is a myeloproliferative disease that mediated by BCR/ABL oncogenic signaling. CML can be targeted with the imatinib, dasatinib, and nilotinib TKI inhibitors, the latter two of them have been approved for imatinib-resistant or -intolerant CML patients. The TKIs resistance occurs by different molecular mechanisms, including overexpression of BCR-ABL, mutations in the TKI binding site of BCR/ABL, and ER-stress. Read More

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A rare cause of persistent leukocytosis with massive splenomegaly: Myeloid neoplasm with BCR-PDGFRA rearrangement-Case report and literature review.

Medicine (Baltimore) 2022 Jun 17;101(24):e29179. Epub 2022 Jun 17.

Department of Hematology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China.

Rationale: Persistent leukocytosis with megalosplenia is a common manifestation among patients with myeloproliferative neoplasm (MPN), especially for chronic myeloid leukemia (CML) patients. Here, we report a rare case of myeloid neoplasm with BCR-PDGFRA rearrangement characterized by obvious elevation of leukocyte count and megalosplenia.

Patient Concerns: A 32-year-old man presented with persistent leukocytosis and megalosplenia. Read More

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Single-cell RNA sequencing to explore composition of peripheral blood NK cells in patients with chronic myeloid leukemia in treatment-free remission.

Leuk Lymphoma 2022 Jun 11:1-12. Epub 2022 Jun 11.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

This study was to explore the role of NK cell subsets and gene expression in maintaining TFR status. We identified six types of NK cells in the PBMCs over both groups (healthy controls and patients with TFR). Gene Oncology analysis showed that up regulated genes were enriched in the categories of "immune response," "reaction to tumor cells," and "cytolysis. Read More

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[Analysis the influence factors of treatment free remission outcome with chronic myeloid leukemia patients who discontinued tyrosine kinase inhibitors].

Zhonghua Yi Xue Za Zhi 2022 May;102(20):1523-1529

Department of Hematology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China.

To explore the related factors affecting the outcome of treatment free remission (TFR) in patients with chronic myeloid leukemia (CML). Clinical data of CML patients with automatic discontinuation of tyrosine kinase inhibitor (TKI) from the CML cooperative organization of Henan province between June 2, 2013 to March 27, 2021 and the follow-up time was ≥ 6 months were retrospectively analyzed. Log-rank test was used for univariate analysis and Cox proportional risk regression model was used for multivariate analysis. Read More

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Vandetanib drives growth arrest and promotes sensitivity to imatinib in chronic myeloid leukemia by targeting ephrin type-B receptor 4.

Mol Oncol 2022 Jun 10. Epub 2022 Jun 10.

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, China.

The oncogenic role of ephrin type-B receptor 4 (EPHB4) has been reported in many types of tumors, including chronic myeloid leukemia (CML). Here, we found that CML patients have a higher EPHB4 expression level than healthy subjects. EPHB4 knockdown inhibited growth of K562 cells (a human immortalized myelogenous leukemia cell line). Read More

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Reduced Cardiotoxicity of Ponatinib-Loaded PLGA-PEG-PLGA Nanoparticles in Zebrafish Xenograft Model.

Materials (Basel) 2022 Jun 2;15(11). Epub 2022 Jun 2.

Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar.

Tyrosine kinase inhibitors (TKIs) are the new generation of anti-cancer drugs with high potential against cancer cells' proliferation and growth. However, TKIs are associated with severe cardiotoxicity, limiting their clinical value. One TKI that has been developed recently but not explored much is Ponatinib. Read More

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Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies.

Cells 2022 05 31;11(11). Epub 2022 May 31.

Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27834, USA.

Glycogen synthase kinase-3 (GSK-3) is an evolutionarily conserved, ubiquitously expressed, multifunctional serine/threonine protein kinase involved in the regulation of a variety of physiological processes. GSK-3 comprises two isoforms (α and β) which were originally discovered in 1980 as enzymes involved in glucose metabolism via inhibitory phosphorylation of glycogen synthase. Differently from other proteins kinases, GSK-3 isoforms are constitutively active in resting cells, and their modulation mainly involves inhibition through upstream regulatory networks. Read More

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[Effects of Dasatinib on the Maturation of Monocyte-Derived Dendritic Cells Derived from Healthy Donors and Chronic Myelogenous Leukemia Patients].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2022 Jun;30(3):677-687

Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, Chengdu 610000, Sichuan Province, China,E-mail:

Objective: To investigate the effects of dasatinib on the maturation of monocyte-derived dendritic cells (moDCs) derived from healthy donors (HDs) and chronic myelogenous leukemia (CML) patients.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=10) and CML patients (n=10) who had got the remission of MR4.5 with imatinib treatment. Read More

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[Dose optimization: an individualized treatment strategy for chronic myeloid leukemia].

Zhonghua Xue Ye Xue Za Zhi 2022 May;43(5):436-440

Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

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Biting into a union of oncology and metabolism through leukemic stem cells.

Cell Metab 2022 Jun;34(6):801-802

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.

In this issue of Cell Metabolism, Liu et al. demonstrate that Prmt7 can regulate the onset and progression of leukemogenesis by inhibiting self-renewal capacity of leukemic stem cells (LSCs) as modeled in a murine version of chronic myeloid leukemia (CML). Read More

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Novel mitochondria-targeting compounds selectively kill human leukemia cells.

Leukemia 2022 Jun 7. Epub 2022 Jun 7.

Department of BioSciences, Rice University, Houston, TX, USA.

Acute myeloid leukemia (AML) is a heterogeneous group of aggressive hematological malignancies commonly associated with treatment resistance, high risk of relapse, and mitochondrial dysregulation. We identified six mitochondria-affecting compounds (PS compounds) that exhibit selective cytotoxicity against AML cells in vitro. Structure-activity relationship studies identified six analogs from two original scaffolds that had over an order of magnitude difference between LD50 in AML and healthy peripheral blood mononuclear cells. Read More

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Determination of the Cut-off Value for Imatinib Plasma Levels Linked to Occurrence of Bone Pain in CML Patients.

Drug Des Devel Ther 2022 30;16:1595-1604. Epub 2022 May 30.

Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

Background: Imatinib is used to treat chronic myelogenous leukemia (CML). Variations in imatinib pharmacokinetics have been linked to genetic variations. That has an impact on imatinib response and adverse effects. Read More

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Abnormal imaging presentations of extramedullary hematopoiesis in a 21-year old and 72-year old female.

Radiol Case Rep 2022 Aug 28;17(8):2619-2625. Epub 2022 May 28.

Department of Radiology, Ascension Providence Hospital-MSU College of Human Medicine Southeast Michigan Campus, 16001 W. Nine Mile Road, Southfield, MI, 48075, USA.

Extramedullary hematopoiesis (EH) refers to hemopoiesis that occurs outside of the bone marrow and can be physiologic or pathologic in nature. Common sites of EH include the liver, spleen, and paravertebral soft tissues. Less commonly, EH can occur in the kidneys, pleura, paranasal sinuses, and various other organs. Read More

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Management of Myeloproliferative Neoplasms in the Molecular Era: From Research to Practice.

Am Soc Clin Oncol Educ Book 2022 Apr;42:1-19

Global Oncology Program and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

The 1960 discovery of the Philadelphia chromosome in chronic myeloid leukemia (CML) marked the beginning of the modern genomic era of oncology. In the following years, the molecular underpinnings of CML were unraveled, culminating in the development of the first molecularly targeted therapy: imatinib. Imatinib revolutionized CML management, inducing deep molecular responses for most patients and aligning survival curves with those of age-matched control participants. Read More

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Brazilian chronic myeloid leukemia working group recommendations for discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia in clinical practice.

Hematol Transfus Cell Ther 2022 May 3. Epub 2022 May 3.

Complexo Hospital de Clínicas, Universidade Federal do Paraná (CHC-UFPR), Curitiba, PR, Brazil.

Introduction: Treatment-free remission (TFR) is a new goal of chronic myeloid leukemia (CML) therapy. TFR is feasible when the patient has achieved a deep and stable molecular response and met the criteria required to ensure its success. Treatment discontinuation should not be proposed to the CML patient if minimum conditions are not met. Read More

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The structural basis of BCR-ABL recruitment of GRB2 in chronic myelogenous leukemia.

Biophys J 2022 Jun 31;121(12):2251-2265. Epub 2022 May 31.

Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, Maryland; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

BCR-ABL drives chronic myeloid leukemia (CML). BCR binding to GRB2 transduces signaling via the Ras/MAPK pathway. Despite considerable data confirming the binding, molecular-level understanding of exactly how the two proteins interact, and, especially, what are the determinants of the specificity of the SH2 domain-phosphorylated BCR (pBCR) recognition are still open questions. Read More

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Activin A downregulates the CD69-MT2A axis via p38MAPK to induce erythroid differentiation that sensitizes BCR-ABL-positive cells to imatinib.

Exp Cell Res 2022 Aug 26;417(2):113219. Epub 2022 May 26.

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan. Electronic address:

Induction of differentiation sensitizes chronic myeloid leukemia (CML) cells to the BCR-ABL inhibitor imatinib by mechanisms that remain unknown. We previously identified the BCR-ABL downstream effector CD69 which inhibits imatinib-induced CML cell differentiation. Herein, we found that the erythroid differentiation inducers activin A and aclacinomycin A induced expression of erythroid markers (α-globin, ζ-globin, GATA-1, and glycophorin A) and simultaneously reduced CD69 levels in K562 CML cells. Read More

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FDA Approval Summary: Revised Indication and Dosing Regimen for Ponatinib Based on the Results of the OPTIC Trial.

Oncologist 2022 03;27(2):149-157

Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.

On December 18, 2020, US Food and Drug Administration (FDA) approved a supplemental application for ponatinib extending the indication in patients with chronic-phase chronic myeloid leukemia (CP-CML) to patients with resistance or intolerance of at least 2 prior kinase inhibitors. Ponatinib was initially approved in December 2012 but was briefly voluntarily withdrawn due to serious safety concerns including the risk of arterial occlusive events (AOE). It returned to the market in December 2013 with an indication limited to patients with T315I mutation or for whom no other tyrosine kinase inhibitor (TKI) therapy was indicated with revised warnings and precautions. Read More

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Novel Tyrosine Kinase Inhibitors to Target Chronic Myeloid Leukemia.

Molecules 2022 May 18;27(10). Epub 2022 May 18.

Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.

This paper reports on a novel series of tyrosine kinase inhibitors (TKIs) potentially useful for the treatment of chronic myeloid leukemia (CML). The newly designed and synthesized compounds are structurally related to nilotinib (NIL), a second-generation oral TKI, and to a series of imatinib (IM)-based TKIs, previously reported by our research group, these latter characterized by a hybrid structure between TKIs and heme oxygenase-1 (HO-1) inhibitors. The enzyme HO-1 was selected as an additional target since it is overexpressed in many cases of drug resistance, including CML. Read More

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Vorinostat Combined with Busulfan, Fludarabine, and Clofarabine Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia: Long-Term Study Outcomes.

Transplant Cell Ther 2022 May 23. Epub 2022 May 23.

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address:

Conditioning regimens play a major role in determining disease outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The use of i.v. Read More

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The Dawn of Allosteric BCR-ABL1 Drugs: From a Phenotypic Screening Hit to an Approved Drug.

J Med Chem 2022 Jun 24;65(11):7581-7594. Epub 2022 May 24.

Department of Chemical and Systems Biology, ChEM-H, Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, California 94305, United States.

Chronic myeloid leukemia (CML) is driven by the constitutive activity of the BCR-ABL1 fusion oncoprotein. Despite the great success of drugs that target the BCR-ABL1 ATP-binding site in transforming CML into a manageable disease, emerging resistance point mutations impair inhibitor binding, thereby limiting the effectiveness of these drugs. Recently, allosteric inhibitors that interact with the ABL1 myristate-binding site have been shown to awaken an endogenous regulatory mechanism and reset full-length BCR-ABL1 into an inactive assembled state. Read More

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6,7-Dimethoxycoumarin Influences the Erythroid Differentiation of Human Chronic Myelogenous Leukemia K562 Cells through Regulating FOXO3/p27 Signal Pathway.

J Oncol 2022 14;2022:1138851. Epub 2022 May 14.

Pharmaceutical Department, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, Jiangsu 226018, China.

Objective: To study the pharmacological activity and the mechanism of action of natural compounds derived from 6,7-dimethoxycoumarin on the differentiation of human chronic myeloid leukemia K562 cells.

Methods: We use MTT assay (Sigma-Aldrich, USA) to detect cell viability; use flow cytometry to analyze DNA content for cell cycle analysis; use benzidine staining to synthesize hemoglobin to determine K562 cell differentiation; use western blot analysis and qPCR to detect the expression levels of FOX03, P27, CDK4, and their phosphorylation; and use the AOBS laser scanning confocal system (Leica, Wetzlar, Germany) to analyze and quantify the number of positive green spots. The statistical methods used are one-way analysis of variance (ANOVA) and Dunnett's test to analyze within and between groups. Read More

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