24,056 results match your criteria bcr-abl


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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A case of a primary myelofibrosis with progression and related literature review of progression phase genetics.

Int J Lab Hematol 2021 Jul;43 Suppl 1:78-81

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Philadelphia (BCR-ABL)-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPN can transform into an accelerated or a blast phase, which is associated with poor response to standard therapy and low overall median survival. We present an interesting case of a patient with a history of PMF and progression and summarize the current studies on genetic features of myeloproliferative neoplasms in blast phase (MPN-BP) with an emphasis on PMF. 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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Reduced eIF4E function impairs B-cell leukemia without altering normal B-lymphocyte function.

iScience 2021 Jul 17;24(7):102748. Epub 2021 Jun 17.

Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA.

The cap-binding protein eukaryotic initiation factor 4E (eIF4E) promotes translation of mRNAs associated with proliferation and survival and is an attractive target for cancer therapeutics. Here, we used germline and conditional knockout models to assess the impact of reduced gene dosage on B-cell leukemogenesis compared to effects on normal pre-B and mature B-cell function. Using a BCR-ABL-driven pre-B-cell leukemia model, we find that loss of one allele of impairs transformation and reduces fitness in competition assays and . 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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Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis.

Mol Cells 2021 Jul 13. Epub 2021 Jul 13.

Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 06974, Korea.

Although the mechanism of chronic myeloid leukemia (CML) initiation through BCR/ABL oncogene has been well characterized, CML cell differentiation into erythroid lineage cells remains poorly understood. Using CRISPR-Cas9 screening, we identify Chromobox 8 (CBX8) as a negative regulator of K562 cell differentiation into erythrocytes. CBX8 is degraded via proteasomal pathway during K562 cell differentiation, which activates the expression of erythroid differentiation-related genes that are repressed by CBX8 in the complex of PRC1. Read More

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BCR-ABL+ Chronic Myeloid Leukemia Arising in a Family With Inherited ANKRD26-Related Thrombocytopenia.

JCO Precis Oncol 2021 19;5. Epub 2021 Feb 19.

Division of Hematology & Medical Oncology, Oregon Health & Science University, Portland, OR.

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February 2021

[Preparation and identification of rabbit polyclonal antibody against BCR-ABL b3a2 fusion protein].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Aug;37(8):746-751

Translational Medicine Institute, Chenzhou Hospital Affiliated to University of South China, Chenzhou 423000; National & Local Joint Engineering Laboratory for High-Through Molecular Diagnosis Technology, Chenzhou Municipal First People's Hospital, Chenzhou 423000; First School of Clinical Medicine, Southern Medical University, Guangzhou 510000, China. *Corresponding author, E-mail:

Objective To prepare and identify rabbit anti-breakpoint cluster region-Abelson leukemia virus oncogene (BCR-ABL) b3a2 subtype polyclonal antibody. Methods A peptide containing the fusion sequence of the b3a2 subtype BCR-ABL fusion protein was designed and synthesized with the purity higher than 90%. The fusion polypeptide was coupled to Keyhole Limpet hemocyanin (KLH) and used to immune New Zealand rabbits. Read More

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Flavonoid derivatives targeting BCR-ABL kinase: Semisynthesis, Molecular dynamic simulations and Enzymatic inhibition.

Curr Top Med Chem 2021 Jul 5. Epub 2021 Jul 5.

Programa de Pós-Graduação em Agroquímica, Universidade Federal do Espírito Santo, 29500000, Alegre - ES , Brazil.

Background: Natural products have been universally approached in the research of novel trends useful to detail the essential paths of the life sciences and as a strategy for pharmacotherapeutics.

Objective: This work focuses on further modification to the 6-hydroxy-flavanone building block aiming to obtain improved BCR-ABL kinase inhibitors.

Methods: Ether derivatives were obtained from Williamson synthesis and triazole from Microwave-assisted click reaction. 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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44-Year-Old Man With Fatigue, Weight Loss, and Leukocytosis.

Mayo Clin Proc 2021 07;96(7):1944-1948

Advisor to residents and Consultant in Hematology, Mayo Clinic, Rochester, MN. Electronic address:

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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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Discovery of novel BCR-ABL PROTACs based on the cereblon E3 ligase design, synthesis, and biological evaluation.

Eur J Med Chem 2021 Jun 25;223:113645. Epub 2021 Jun 25.

Shanghai Institute for Advanced Immunochemical Studies, China; CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China. Electronic address:

Protein degradation is a promising strategy for drug development. Proteolysis-targeting chimeras (PROTACs) hijacking the E3 ligase cereblon (CRBN) exhibit enormous potential and universal degradation performance due to the small molecular weight of CRBN ligands. In this study, the CRBN-recruiting PROTACs were explored on the degradation of oncogenic fusion protein BCR-ABL, which drives the pathogenesis of chronic myeloid leukemia (CML). Read More

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Exploiting polypharmacology to dissect host kinases and kinase inhibitors that modulate endothelial barrier integrity.

Cell Chem Biol 2021 Jun 29. Epub 2021 Jun 29.

Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA; Department of Pediatrics, University of Washington, Seattle, WA 98105, USA. Electronic address:

Kinase inhibitors are promising drugs to stabilize the endothelial barrier following inflammatory damage. However, our limited knowledge of how kinase signaling activates barrier-restorative pathways and the complexity of multi-target drugs have hindered drug discovery and repurposing efforts. Here, we apply a kinase regression approach that exploits drug polypharmacology to investigate endothelial barrier regulation. 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

Priapism in Patients with Chronic Myeloid Leukemia (CML): A Systematic Review.

Acta Biomed 2021 07 1;92(3):e2021193. Epub 2021 Jul 1.

Medical Oncology, Hematology Section, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar.

Background: Priapism is defined as a penile erection that persists four or more hours and is unrelated to sexual stimulation. Priapism resulting from hematologic malignancy is most likely caused by venous obstruction from microemboli/thrombi and hyperviscosity caused by the increased number of circulating leukocytes in mature and immature forms. In patients with leukemia, 50% of cases of priapism are due to Chronic Myeloid Leukemia (CML). Read More

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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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The Prevalence of Gene Mutations in Patients with --Negative Myeloproliferative Neoplasms (MPN): A Systematic Review and Meta-Analysis.

Cancers (Basel) 2021 Jun 20;13(12). Epub 2021 Jun 20.

Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.

Multiple recurrent somatic mutations have recently been identified in association with myeloproliferative neoplasms (MPN). This meta-analysis aims to assess the pooled prevalence of gene mutations among patients with MPN. Six databases (PubMed, Scopus, ScienceDirect, Google Scholar, Web of Science and Embase) were searched for relevant studies from inception till September 2020, without language restrictions. Read More

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High-Throughput Human Telomere Length Analysis at the Single-Chromosome Level by FISH Coupled with Nano-Flow Cytometry.

Anal Chem 2021 07 1;93(27):9531-9540. Epub 2021 Jul 1.

Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory for Chemical Biology of Fujian Province, Collaborative Innovation Center of Chemistry for Energy Materials, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, PR China.

Telomere length (TL) is a highly relevant biomarker for age-associated diseases and cancer, yet its clinical applications have been hindered by the inability of existing methods to rapidly measure the TL distribution and the percentage of chromosomes with critically short telomeres (CSTs, < 3 kb). Herein, we report the development of a high-throughput method to measure TL at the single-chromosome level. Metaphase chromosomes are isolated, hybridized with the Alexa Fluor 488-labeled telomeric peptide nucleic acid probe, and analyzed using a laboratory-built ultrasensitive nano-flow cytometer. Read More

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Distinguishing Isolated Lymphoid Extramedullary Blast Crisis and Secondary Non-Hodgkin Lymphoma in Chronic Myelogenous Leukemia: a Case Report and Review of the Literature.

Iran J Immunol 2021 Jun;18(2):141-145

Department of International Medical Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

Extramedullary blast crisis (EBC) is a special kind of blast crisis of chronic myelogenous leukemia (CML). It is more likely to be misdiagnosed as lymphoma when EBC cells are of lymphoid cell lineage and lymphadenopathy is the only symptom before the final diagnosis. In this study, we presented a patient with an unusual presentation of CML transformation as a rapid growth of generalized lymphadenopathy that appeared 5 months after the initial diagnosis of CML. 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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Characteristics of BCR-ABL gene variants in patients of chronic myeloid leukemia.

Open Med (Wars) 2021 23;16(1):904-912. Epub 2021 Jun 23.

Department of Pathology, Islamic International Medical College, Rawalpindi, Pakistan.

Background: Depending on breakpoints of rearrangement different types of BCR-ABL fusion protein can be generated in patients of chronic myeloid leukemia (CML). The aim of this study is to observe frequencies of major transcripts in CML patients by reverse transcriptase polymerase chain reaction (RT-PCR) and their hematological features at the time of presentation.

Materials And Methods: This cross sectional study was performed at Molecular Lab of Riphah International University, Islamabad from January to June 2019. 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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["New treatments for chronic myelogenous leukemia"].

Rev Prat 2021 Mar;71(3):245-248

"Service d'hématologie clinique, hôpital Paul-Brousse, AP-HP, université Paris-Saclay, Villejuif, France".

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T lymphoblastic lymphoma with BCR-ABL negative chronic myeloid leukaemia: a novel association.

Ecancermedicalscience 2021 22;15:1221. Epub 2021 Apr 22.

Department of Histopathology, The Children's Hospital & Institute of Child Health, Ferozepur Road, Lahore 54400, Pakistan.

Lymphoblastic lymphoma and chronic myeloid leukaemia (CML) are two distinct neoplasms with different pathogenesis and clinical presentation. We hereby share a challenging case of a child presenting with fever, leucocytosis, generalised lymphadenopathy and massive splenomegaly. He was diagnosed as having novel association of concurrent T-lymphoblastic lymphoma diagnosed on cervical lymph node biopsy with BCR-ABL negative CML on bone marrow aspirate. 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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