6,630 results match your criteria bcr-abl tyrosine


Spectrum of BCR-ABL Mutations and Treatment Outcomes in Ethiopian Imatinib-Resistant Patients With Chronic Myeloid Leukemia.

JCO Glob Oncol 2021 Jul;7:1187-1193

Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: Despite the successes achieved in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy, resistance remains an obstacle. The most common mechanism of resistance is the acquisition of a point mutation in the BCR-ABL kinase domain. Few studies have reported African patients with CML in regard to such mutations. Read More

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Comparison of Hepatotoxicity Associated With New BCR-ABL Tyrosine Kinase Inhibitors vs Imatinib Among Patients With Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis.

JAMA Netw Open 2021 Jul 1;4(7):e2120165. Epub 2021 Jul 1.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China.

Importance: Although BCR-ABL fusion oncoprotein tyrosine kinase inhibitors (BCR-ABL TKIs) can substantially improve the survival rate of chronic myeloid leukemia (CML), they are clinically accompanied by severe hepatotoxicity.

Objective: To compare the relative risk (RR) of hepatotoxicity of new-generation BCR-ABL TKIs with that of imatinib, and to provide an overall assessment of the clinical benefit.

Data Sources: PubMed, Embase, Cochrane library databases, and ClinicalTrials. Read More

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Cardiovascular Issues in Tyrosine Kinase Inhibitors Treatments for Chronic Myeloid Leukemia: A Review.

Front Physiol 2021 5;12:675811. Epub 2021 Jul 5.

Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by a fusion gene, encoding for the chimeric protein BCR-ABL, with constitutive tyrosine kinase activity. The use of tyrosine kinase inhibitors (TKIs) has drastically improved survival, but there are significant concerns about cardiovascular toxicity. Cardiovascular risk can be lowered with appropriate baseline evaluation, accurate choice of TKI therapy, improvement of modifiable cardiovascular risk factors through lifestyle modifications, and prescription of drugs for primary or secondary prevention. Read More

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Cardiovascular events and atherogenic lipid profile in chronic myeloid leukemia patients treated with nilotinib versus imatinib.

Bratisl Lek Listy 2021 ;122(8):531-537

Objectives: The aim of this study was to assess cardiotoxicity and potential adverse effects related to lipid metabolism during treatment with tyrosine kinase inhibitors (TKIs) imatinib and nilotinib in patients with chronic myeloid leukemia (CML).

Patients And Methods: Eighty-two consecutive patients with CML, who received nilotinib and/or imatinib in a single haemato-oncological Slovak center between years 2002-2018 were evaluated in a retrospective study. The mean age was 55. Read More

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Generation of the induced pluripotent stem cell line KUMi001-A carrying the Philadelphia chromosome from a chronic myeloid leukemia patient.

Stem Cell Res 2021 Jul 12;55:102464. Epub 2021 Jul 12.

Institute of Stem Cell Research, Korea University College of Medicine, Seoul, South Korea; Department of Biomedical and Science, Graduate School of Medicine, Korea University, Seoul, South Korea; Department of Internal Medicine, Korea University Medical School Hospital, Seoul, South Korea. Electronic address:

Chronic myeloid leukemia (CML) is caused by the BCR-ABL fusion protein, which dysregulates tyrosine kinase activity. In this study, we generated induced pluripotent stem cells (iPSCs) carrying the Philadelphia chromosome from a CML patient with the BCR-ABL fusion protein. CML iPSCs were positive for pluripotency markers and had the ability to differentiate into the three germ layers. Read More

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Clinico-laboratory pertinences and management of relapsed and refractory.

Authors:
Vasile Musteata

J BUON 2021 May-Jun;26(3):1165-1168

State University of Medicine and Pharmacy "N. Testemitanu", Institute of Oncology.

Purpose: The purpose of this study was to assess the biological significance of lactate dehydrogenase (LDH), T315I mutation and treatment options in newly diagnosed and relapsed patients with chronic myeloid leukemia (CML).

Methods: Our clinical-analytical and descriptive study enrolled 27 patients with different phases of CML, who were followed up and treated at the Institute of Oncology between 1995-2020. Venous blood samples were taken for LDH measurement, molecular screening and detection of T315I mutation of the ABL gene in order to investigate the biological significance of the increased LDH values and T315I mutation. Read More

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Pharmacogenomics of Impaired Tyrosine Kinase Inhibitor Response: Lessons Learned From Chronic Myelogenous Leukemia.

Front Pharmacol 2021 28;12:696960. Epub 2021 Jun 28.

Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Kiel, Germany.

The use of small molecules became one key cornerstone of targeted anti-cancer therapy. Among them, tyrosine kinase inhibitors (TKIs) are especially important, as they were the first molecules to proof the concept of targeted anti-cancer treatment. Since 2001, TKIs can be successfully used to treat chronic myelogenous leukemia (CML). Read More

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[Chronic myeloid leukemia: aiming for treatment free remission].

Authors:
Shinya Kimura

Rinsho Ketsueki 2021 ;62(6):572-581

Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University.

BCR-ABL tyrosine kinase inhibitors (TKIs) dramatically improve the chronic myeloid leukemia (CML) prognosis, and most CML patients in the chronic phase are now able to lead lives that are comparable to those of healthy individuals. However, the high cost and adverse effects associated with long-term treatment remain issues in the treatment of CML patients. At the setout, a clinical study involving the discontinuation of imatinib was conducted in France. Read More

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Effect of HSP90AB1 and CC domain interaction on Bcr-Abl protein cytoplasm localization and function in chronic myeloid leukemia cells.

Cell Commun Signal 2021 Jul 3;19(1):71. Epub 2021 Jul 3.

Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated By Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.

Background: The fusion oncoprotein Bcr-Abl is mostly located in the cytoplasm, which causes chronic myeloid leukemia (CML). After moving into the nucleus, the fusion protein can induce apoptosis of CML cells. The coiled-coil domain (CC domain) of Bcr-Abl protein plays a central role in the subcellular localization. Read More

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Cryptotanshinone enhances the efficacy of Bcr-Abl tyrosine kinase inhibitors via inhibiting STAT3 and eIF4E signalling pathways in chronic myeloid leukaemia.

Pharm Biol 2021 Dec;59(1):893-903

The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

Context: A portion of patients with chronic myeloid leukaemia (CML) develop resistance to the Bcr-Abl tyrosine kinase inhibitors (TKIs), limiting the clinical applications. Previous results have demonstrated the synergistic effects between cryptotanshinone (CPT) and imatinib on apoptosis of CML cells .

Objective: To determine the antileukemia effects of CPT and TKIs on the resistant CML cells, and further investigate the effect of combined treatment of CPT and imatinib on tumour growth and apoptosis in the xenograft model and clarify its regulatory mechanisms. Read More

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December 2021

Targeting Leukemic Stem Cells in Chronic Myeloid Leukemia: Is It Worth the Effort?

Int J Mol Sci 2021 Jun 30;22(13). Epub 2021 Jun 30.

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", 40138 Bologna, Italy.

Chronic myeloid leukemia (CML) is a classical example of stem cell cancer since it arises in a multipotent hematopoietic stem cell upon the acquisition of the t(9;22) chromosomal translocation, that converts it into a leukemic stem cell (LSC). The resulting fusion gene encodes a deregulated tyrosine kinase that is recognized as the disease driver. Therapy with tyrosine kinase inhibitors (TKIs) eliminates progenitor and more differentiated cells but fails to eradicate quiescent LSCs. Read More

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Understanding and Monitoring Chronic Myeloid Leukemia Blast Crisis: How to Better Manage Patients.

Cancer Manag Res 2021 23;13:4987-5000. Epub 2021 Jun 23.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Chronic myeloid leukemia (CML) is triggered primarily by the t(9;22) (q34.13; q11.23) translocation. Read More

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The c-Abl inhibitor, radotinib induces apoptosis in multiple myeloma cells via mitochondrial-dependent pathway.

Sci Rep 2021 Jun 24;11(1):13198. Epub 2021 Jun 24.

Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 44033, Republic of Korea.

Multiple myeloma (MM) is a hematological cancer resulting from accumulated abnormal plasma cells. Unfortunately, MM remains an incurable disease, as relapse is very common. Therefore, there is urgent need to develop new treatment options for MM. Read More

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Targeting HSPA8 inhibits proliferation via downregulating BCR-ABL and enhances chemosensitivity in imatinib-resistant chronic myeloid leukemia cells.

Exp Cell Res 2021 Jun 19;405(2):112708. Epub 2021 Jun 19.

Department of Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, PR China.

The resistance to tyrosine kinase inhibitors is currently a major problem for chronic myeloid leukemia (CML) treatment and HSPA8 is highly expressed and a hallmark of poor prognosis in several human cancers. However, its role in imatinib-resistant CML (IR-CML) cells remains undetermined. Here, we determined HSPA8 was overexpressed in IR-CML cells and associated with imatinib resistance. Read More

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CXCR2, a novel target to overcome tyrosine kinase inhibitor resistance in chronic myelogenous leukemia cells.

Biochem Pharmacol 2021 Jun 17;190:114658. Epub 2021 Jun 17.

Department of Internal Medicine, Anam Hospital Korea University Medical Center, Seoul, South Korea. Electronic address:

Chronic myeloid leukemia (CML) is a reciprocal translocation disorder driven by a breakpoint cluster region (BCR)-Abelson leukemia virus (ABL) fusion gene that stimulates abnormal tyrosine kinase activity. Tyrosine kinase inhibitors (TKIs) are effective in treating Philadelphia chromosome (Ph) + CML patients. However, the appearance of TKI-resistant CML cells is a hurdle in CML treatment. Read More

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Nilotinib-induced bone marrow CD34+/lin-Ph+ cells early clearance in newly diagnosed CP-Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study.

Eur J Haematol 2021 Jun 17. Epub 2021 Jun 17.

Division of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy.

Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph-chromosome and the BCR-ABL tyrosine-kinase (TK). Target-therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second-generation TKI Nilotinib. Read More

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Italian Real-World Analysis of a Tyrosine Kinase Inhibitor Administration as First- or Second-Line of Therapy in Patients with Chronic Myeloid Leukemia.

Ther Clin Risk Manag 2021 8;17:617-622. Epub 2021 Jun 8.

CliCon S.r.l. Health, Economics & Outcomes Research, Bologna, Italy.

Purpose: To date, litte evidence is reported about the real-life dosage of tyrosine kinase inhibitors prescribed in Italy. The present observational retrospective study aimed to evaluate the mean daily dose of nilotinib prescribed as first- and second-line therapy among patients suffering from chronic myeloid leukemia (CML) in settings of clinical practice in Italy.

Patients And Methods: Data were obtained from the administrative databases of a sample of Italian entities. Read More

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Electronic and structural study of T315I mutated form in DFG-out conformation of BCR-ABL inhibitors.

J Biomol Struct Dyn 2021 Jun 14:1-15. Epub 2021 Jun 14.

Institute of Chemistry, Laboratory of Computational Chemistry, University of Brasília, Brasília, Federal District, Brazil.

In this work, the four main drugs for the treatment of chronic myeloid leukemia were analyzed, being imatinib, dasatinib, nilotinib and ponatinib followed by four derivative molecules of nilotinib and ponatinib. For these derivative molecules, the fluorine atoms were replaced by hydrogen and chlorine atoms in order to shade light to the structural effects on this set of inhibitors. Electronic studies were performed at density functional theory level with the B3LYP functional and 6-311+G(d,p) basis set. Read More

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Metabolic alterations mediated by STAT3 promotes drug persistence in CML.

Leukemia 2021 Jun 12. Epub 2021 Jun 12.

Department of Medicine, Division of Hematology/Oncology, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.

Leukemic stem cells (LSCs) can acquire non-mutational resistance following drug treatment leading to therapeutic failure and relapse. However, oncogene-independent mechanisms of drug persistence in LSCs are incompletely understood, which is the primary focus of this study. We integrated proteomics, transcriptomics, and metabolomics to determine the contribution of STAT3 in promoting metabolic changes in tyrosine kinase inhibitor (TKI) persistent chronic myeloid leukemia (CML) cells. Read More

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Cabozantinib promotes erythroid differentiation in K562 erythroleukemia cells through global changes in gene expression and JNK activation.

Cancer Gene Ther 2021 Jun 11. Epub 2021 Jun 11.

Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.

Cabozantinib is a potent tyrosine kinase inhibitor with multiple targets including MET, VEGFR2, RET, KIT, and FLT3. Cabozantinib is widely used for the treatment of medullary thyroid cancer and renal cell carcinoma. We recently suggested cabozantinib as a potential therapeutic alternative for acute myeloid leukemia (AML) patients with FLT3-internal tandem duplication (FLT3-ITD). Read More

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IMiDs uniquely synergize with TKIs to upregulate apoptosis of Philadelphia chromosome-positive acute lymphoblastic leukemia cells expressing a dominant-negative IKZF1 isoform.

Cell Death Discov 2021 Jun 11;7(1):139. Epub 2021 Jun 11.

Department of Pediatrics, Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.

The long-term prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is still unsatisfactory even after the emergence of tyrosine kinase inhibitors (TKIs) against chimeric BCR-ABL, and this is associated with the high incidence of genetic alterations of Ikaros family zinc finger 1 (IKZF1), most frequently the hemi-allelic loss of exons 4-7 expressing a dominant-negative isoform Ik6. We found that lenalidomide (LEN), a representative of immunomodulatory drugs (IMiDs), which have been long used for the treatment of multiple myeloma, specifically induced accumulation of Ik6 with the disappearance of functional isoforms within 24 h (i.e. Read More

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Assessment of droplet digital polymerase chain reaction for measuring BCR-ABL1 in chronic myeloid leukaemia in an international interlaboratory study.

Br J Haematol 2021 Jul 10;194(1):53-60. Epub 2021 Jun 10.

Faculty of Medicine Dentistry and Health, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.

Measurement of BCR activator of RhoGEF and GTPase -ABL proto-oncogene 1, non-receptor tyrosine kinase (BCR-ABL1) mRNA levels by reverse transcription quantitative polymerase chain reaction (RTqPCR) has been critical to treatment protocols and clinical trials in chronic myeloid leukaemia; however, interlaboratory variation remains a significant issue. Reverse transcriptase droplet digital PCR (RTddPCR) has shown potential to improve testing but a large-scale interlaboratory study is required to definitively establish this. In the present study, 10 BCR-ABL1-positive samples with levels ranging from molecular response (MR) -MR were tested by 23 laboratories using RTddPCR with the QXDX BCR-ABL %IS kit. Read More

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Brefeldin A Induces Apoptosis, Inhibits BCR-ABL Activation, and Triggers BCR-ABL Degradation in Chronic Myeloid Leukemia K562 Cells.

Anticancer Agents Med Chem 2021 Jun 8. Epub 2021 Jun 8.

Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by BCR-ABL oncoprotein. Tyrosine kinase inhibitors have been developed to inhibit the activity of BCR-ABL; however, drug resistance and side effect occur in clinic application. Therefore, it is urgent to find novel drugs for CML treatment. Read More

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Implementation of DoE and Risk-Based Enhanced Analytical Quality by Design Approach to Stability Indicating RP-HPLC Method for Stability Study of Bosutinib.

J AOAC Int 2021 Jun 8. Epub 2021 Jun 8.

Department of Quality Assurance, Maliba Pharmacy College, UkaTarsadia University, Bardoli-Mahuva Road, Tarsadi, Mahuva, Surat-394 350, Gujarat, India.

Background: Bosutinib is a small molecule BCR-ABL, and src tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukaemia. According to published literature, no stability-indicating RP-HPLC method has been reported yet for estimation of bosutinib.

Objective: Hence, the stability-indicating RP-HPLC method has been developed for the stability study of bosutinib using risk and DoE-based enhanced analytical quality by design approach. Read More

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Nilotinib-Associated Atherosclerosis Presenting as Multifocal Intracranial Stenosis and Acute Stroke.

J Stroke Cerebrovasc Dis 2021 Aug 2;30(8):105883. Epub 2021 Jun 2.

Department of Neurology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ, United States.

Nilotinib, a BCR-ABL tyrosine kinase inhibitor (TKI), has been associated with vascular events and accelerated arterial stenosis, presumably of atherosclerotic etiology. Studies of nilotinib-associated atherosclerosis are mainly associated with progressive peripheral artery occlusive disease (PAOD), and only a few cases of coronary artery disease (CAD), and cerebrovascular disease (CVD) have been reported. The mechanisms by which nilotinib promotes atherosclerosis are poorly understood but endothelial and perivascular factors, mast cell depletion, and metabolic factors such as promotion of dyslipidemia and impaired glucose metabolism are thought to play a role. Read More

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Screening and identification of key genes in imatinib-resistant chronic myelogenous leukemia cells: a bioinformatics study.

Hematology 2021 Dec;26(1):408-414

State Key Laboratory of Fine Chemicals, School of Life Science and Technology, Dalian University of Technology, Dalian, People's Republic of China.

Background: Chronic myelogenous leukemia (CML) is one of the most common cancers in the world. Imatinib is one of the most effective therapeutic strategies to inhibit the BCR-ABL tyrosine Kinase in patients with CML, but resistance is increasingly encountered.

Material And Methods: Microarray data GSE7114, GSE92624 and GSE97562 were downloaded and analyzed from Gene Expression Omnibus (GEO) to identify the candidate genes in the imatinib-resistant CML cells. Read More

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December 2021

Synthesis and antileukemic activity of an ursolic acid derivative: A potential co-drug in combination with imatinib.

Chem Biol Interact 2021 Aug 26;344:109535. Epub 2021 May 26.

Laboratory of Phytochemistry and Organic Synthesis, Graduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil. Electronic address:

Imatinib, a specific Bcr-Abl tyrosine kinase inhibitor, is the most commonly used drug in the treatment of chronic myeloid leukemia. However, optimal response is not achieved in up to 33% of patients. Therefore, development of novel therapeutic strategies for chronic myeloid leukemia is critical. Read More

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Development of a cobalt(iii)-based ponatinib prodrug system.

Inorg Chem Front 2021 Mar 30;8(10):2468-2485. Epub 2021 Mar 30.

Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna Waehringer Straße 42 1090 Vienna Austria.

Receptor tyrosine kinase inhibitors have become a central part of modern targeted cancer therapy. However, their curative potential is distinctly limited by both rapid resistance development and severe adverse effects. Consequently, tumor-specific drug activation based on prodrug designs, exploiting tumor-specific properties such as hypoxic oxygen conditions, is a feasible strategy to widen the therapeutic window. Read More

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A unique three-way Philadelphia chromosome variant t(4;9;22)(q21;q34;q11.2) in a newly diagnosed patient with chronic phase chronic myeloid leukemia: a case report and review of the literature.

J Med Case Rep 2021 May 25;15(1):285. Epub 2021 May 25.

Department of Internal Medicine III, Division of Hematology and Cell Therapy, Yamagata University faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.

Background: Chronic myeloid leukemia is a hematologic malignancy associated with the fusion of two genes: BCR and ABL1. This fusion results from a translocation between chromosomes 9 and 22, which is called the Philadelphia chromosome. Although the Philadelphia chromosome is present in more than 90% of patients with chronic myeloid leukemia, 5-8% of patients with chronic myeloid leukemia show complex variant translocations. Read More

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Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia.

Nat Commun 2021 05 14;12(1):2833. Epub 2021 May 14.

Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. Read More

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