148 results match your criteria discovered bcr-abl

Targeting FEN1 Suppresses the Proliferation of Chronic Myeloid Leukemia Cells Through Regulating Alternative End-Joining Pathways.

DNA Cell Biol 2021 Jun 22. Epub 2021 Jun 22.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Chronic myeloid leukemia (CML) is characterized by the formation of the fusion gene. The BCR-ABL protein leads to an increased level of reactive oxygen species, which is a major cause of endogenous DNA double-strand breaks (DSBs). CML cells are prone to rely on a highly mutagenic alternative end-joining (Alt-EJ) pathway to cope with enhanced DSBs, which aggravates chromosomal instability. 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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Mutational landscape of chronic myeloid leukemia: more than a single oncogene leukemia.

Leuk Lymphoma 2021 May 4:1-15. Epub 2021 May 4.

Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.

The fusion gene, which causes aberrant kinase activity and uncontrolled cell proliferation, is the hallmark of chronic myeloid leukemia (CML). The development of tyrosine kinase inhibitors (TKI) that target the BCR-ABL oncoprotein has led to dramatic improvement in CML management. However, some challenges remain to be addressed in the TKI era, including patient stratification and the selection of frontline TKIs and CML progression. Read More

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Nanocrystal-loaded liposome for targeted delivery of poorly water-soluble antitumor drugs with high drug loading and stability towards efficient cancer therapy.

Int J Pharm 2021 Apr 27;599:120418. Epub 2021 Feb 27.

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, PR China; Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, PR China; Precision Medicine Research Laboratory of Anhui Province, Hefei 230088, PR China; Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, PR China. Electronic address:

Nanocrystals (NCs) enable the delivery of poorly water-soluble drugs with improved dissolution and bioavailability. However, their uncontrolled release and instability make targeted delivery challenging. Herein, a nano-in-nano delivery system composed of a drug nanocrystal core and liposome shell ([email protected]) is presented, which merges the advantages of drug nanocrystals (high drug loading) and liposomes (easy surface functionalization and high stability) for targeted delivery of hydrophobic drugs to tumors. Read More

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Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product function.

Cell Chem Biol 2021 04 28;28(4):559-566.e15. Epub 2021 Jan 28.

Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Novartis-Berkeley Center for Proteomics and Chemistry Technologies, Cambridge, MA 02139, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, Univerity of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, Berkeley, CA 94720, USA. Electronic address:

The translation of functionally active natural products into fully synthetic small-molecule mimetics has remained an important process in medicinal chemistry. We recently discovered that the terpene natural product nimbolide can be utilized as a covalent recruiter of the E3 ubiquitin ligase RNF114 for use in targeted protein degradation-a powerful therapeutic modality within modern-day drug discovery. Using activity-based protein profiling-enabled covalent ligand-screening approaches, here we report the discovery of fully synthetic RNF114-based recruiter molecules that can also be exploited for PROTAC applications, and demonstrate their utility in degrading therapeutically relevant targets, such as BRD4 and BCR-ABL, in cells. Read More

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A case report of lineage switch from T-cell acute leukemia to B-cell acute leukemia.

Medicine (Baltimore) 2020 Oct;99(44):e22490

Jining NO. 1 People's Hospital.

Rationale: ALL is the most common form of leukemia (75% to 80%), it is characterized by clonal expansion of the lymphoid blasts in bone marrow, blood, and other tissues, which can be divided into T lineage and B lineage. Although relapse of acute leukemia is common, a change of immunophenotype at relapse only occurs rarely. Some of these cases have been labeled "lineage switch". Read More

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October 2020

Checkpoint kinase‑1 inhibition and etoposide exhibit a strong synergistic anticancer effect on chronic myeloid leukemia cell line K562 by impairing homologous recombination DNA damage repair.

Oncol Rep 2020 Nov 7;44(5):2152-2164. Epub 2020 Sep 7.

East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.

Leukemia, a malignant hematological disease, has poor therapeutic outcomes due to chemotherapeutic resistance. Increasing evidence has confirmed that the elevated capacity for DNA damage repair in cancer cells is a major mechanism of acquired chemotherapeutic resistance. Thus, combining chemotherapy with inhibitors of DNA damage repair pathways is potentially an ideal strategy for treating leukemia. Read More

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November 2020

Dasatinib-induced colitis: discovering the side effects of immunotherapy.

Rev Esp Enferm Dig 2020 Aug;112(8):663-664

Aparato Digestivo, Hospital Universitario Central de Asturias, España.

The effects of immunotherapy are numerous and are still being discovered. We present a case report of a patient who received dasatinib for chronic myeloid leukemia. A colonoscopy was performed due to a positive fecal occult blood test and colitis was observed. Read More

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DiNeR: a Differential graphical model for analysis of co-regulation Network Rewiring.

BMC Bioinformatics 2020 Jul 2;21(1):281. Epub 2020 Jul 2.

Computational Biology and Bioinformatics Program, Yale University, New Haven, CT, 06520, USA.

Background: During transcription, numerous transcription factors (TFs) bind to targets in a highly coordinated manner to control the gene expression. Alterations in groups of TF-binding profiles (i.e. Read More

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A Nimbolide-Based Kinase Degrader Preferentially Degrades Oncogenic BCR-ABL.

ACS Chem Biol 2020 07 25;15(7):1788-1794. Epub 2020 Jun 25.

Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, United States.

Targeted protein degradation (TPD) and proteolysis-targeting chimeras (PROTACs) have arisen as powerful therapeutic modalities for degrading specific proteins in a proteasome-dependent manner. However, a major limitation of TPD is the lack of E3 ligase recruiters. Recently, we discovered the natural product nimbolide as a covalent recruiter for the E3 ligase RNF114. Read More

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Discovery of Berberine that Targetedly Induces Autophagic Degradation of both BCR-ABL and BCR-ABL T315I through Recruiting LRSAM1 for Overcoming Imatinib Resistance.

Clin Cancer Res 2020 08 25;26(15):4040-4053. Epub 2020 Feb 25.

Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou, China.

Purpose: Imatinib, the breakpoint cluster region protein (BCR)/Abelson murine leukemia viral oncogene homolog (ABL) inhibitor, is widely used to treat chronic myeloid leukemia (CML). However, imatinib resistance develops in many patients. Therefore, new drugs with improved therapeutic effects are urgently needed. Read More

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Histone lysine demethylase KDM5B maintains chronic myeloid leukemia via multiple epigenetic actions.

Exp Hematol 2020 02 30;82:53-65. Epub 2020 Jan 30.

Institute of Basic Medical Sciences, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China; Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China. Electronic address:

The histone lysine demethylase KDM5 family is implicated in normal development and stem cell maintenance by epigenetic modulation of histone methylation status. Deregulation of the KDM5 family has been reported in various types of cancers, including hematological malignancies. However, their transcriptional regulatory roles in the context of leukemia remain unclear. Read More

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February 2020

Intraocular infiltration of Philadelphia chromosome-positive acute lymphoblastic leukemia diagnosed by polymerase chain reaction from the aqueous humor: A case report.

Medicine (Baltimore) 2020 Jan;99(4):e18872

Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.

Rationale: Intraocular manifestation of hematopoietic tumors is rare and often difficult to distinguish from inflammation. We report a patient with acute lymphoblastic leukemia (ALL) who developed intraocular infiltration during the remission period.

Patient Concerns: A 40-year-old man presented with hypopyon in his right eye. Read More

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January 2020

Rearrangement of PDGFRβ gene in a patient with Ph-negative chronic myeloid leukemia t(5;12)(q33;p13) in imatinib mesylate treatment-free remission: a case report.

Int J Clin Exp Pathol 2019 1;12(6):2284-2287. Epub 2019 Jun 1.

Department of Hematology, The First People's Hospital of Yichang, China Three Gorges University Yichang, Hubei, China.

Chronic myeloid leukemia (CML) is a hematologic malignancy, in which more than 95% of CML patients are discovered with the Philadelphia chromosome (Ph) or BCR-ABL rearrangement. Those patients mainly suffer from CML, associating with lack of tyrosine kinase activity and BCR-ABL fusion gene. Here, we reported a patient with Ph-negative CML t(5;12)(q33;p13), accompanying with a rare genetic fusion between the TEL and PDGFRβ genes. Read More

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A Novel Inhibitor of STAT5 Signaling Overcomes Chemotherapy Resistance in Myeloid Leukemia Cells.

Cancers (Basel) 2019 Dec 17;11(12). Epub 2019 Dec 17.

LNOx, GICC, CNRS ERL 7001, University of Tours, 37000 Tours, France.

Signal transducers and activators of transcription 5A and 5B (STAT5A and STAT5B) are crucial downstream effectors of tyrosine kinase oncogenes (TKO) such as BCR-ABL in chronic myeloid leukemia (CML) and FLT3-ITD in acute myeloid leukemia (AML). Both proteins have been shown to promote the resistance of CML cells to tyrosine kinase inhibitors (TKI) such as imatinib mesylate (IM). We recently synthesized and discovered a new inhibitor (17f) with promising antileukemic activity. Read More

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December 2019

MicroRNA-582-3p negatively regulates cell proliferation and cell cycle progression in acute myeloid leukemia by targeting cyclin B2.

Cell Mol Biol Lett 2019 4;24:66. Epub 2019 Dec 4.

5Department of Hematology, The First Hospital of Hunan University of Chinese Medicine, 95 Shaoshan Middle Road, Changsha City, 410007 Hunan Province China.

Background: MicroRNAs (miRNAs) function as post-transcriptional gene expression regulators. Some miRNAs, including the recently discovered miR-582-3p, have been implicated in leukemogenesis. This study aimed to reveal the biological function of miR-582-3p in acute myeloid leukemia (AML), which is one of the most frequently diagnosed hematological malignancies. Read More

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Comparison of chronic myeloid leukemia stem cells and hematopoietic stem cells by global proteomic analysis.

Biochem Biophys Res Commun 2020 02 22;522(2):362-367. Epub 2019 Nov 22.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the standard first-line therapy for patients with chronic-phase CML. However, TKIs cannot eliminate quiescent leukemia stem cells (LSCs) which persist in all patients on long-term therapy and provides a reservoir for disease progression and recurrence. Many researches have confirmed that TKI-resistant LSCs compartment can be captured within CD26  fraction. Read More

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February 2020

[Pathogenesis of thrombosis in JAK2V617F myeloproliferative neoplasms].

Med Sci (Paris) 2019 Aug-Sep;35(8-9):651-658. Epub 2019 Sep 18.

CHU de Bordeaux, Laboratoire d'hématologie, 1, avenue de Magellan, F-33600, Pessac, France. - Univ. Bordeaux, Inserm, UMR 1034, Biologie des maladies cardio-vasculaires, 1, avenue de Magellan, F-33600, Pessac, France.

BCR-ABL negative myeloproliferative neoplasms are acquired hematologic diseases characterized by blood cell proliferation and that include polycythemia vera (PV), essential thrombocytemia (ET) and primary myelofibrosis (PMF). Occurring of venous and arterial thrombosis is the main complication of these diseases. Risk factors for thrombosis are individuals older than 60 and history of thrombosis. Read More

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February 2020

Histone demethylase RBP2 mediates the blast crisis of chronic myeloid leukemia through an RBP2/PTEN/BCR-ABL cascade.

Cell Signal 2019 11 30;63:109360. Epub 2019 Jul 30.

Department of Hematology, Qilu Hospital, Shandong University, No. 107,Wenhua Xi Road, Jinan 250012, Shandong, PR China. Electronic address:

Epigenetic disorders play a key role in tumorigenesis and development, among which histone methylation abnormalities are common. While patients living with chronic myeloid leukemia in the chronic phase (CML-CP) have a good response to TKI, blastic phase (CML-BP) patients demonstrate poor efficacy and high fatality rates. However, while the mechanism of blast crisis of chronic myeloid leukemia remains unclear, high expression and activation of BCR-ABL are usually related to CML blast crisis transition. Read More

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November 2019

BCR: a promiscuous fusion partner in hematopoietic disorders.

Oncotarget 2019 Apr 12;10(28):2738-2754. Epub 2019 Apr 12.

Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA.

Considerable advances have been made in our understanding of the molecular basis of hematopoietic cancers. The discovery of the BCR-ABL fusion protein over 50 years ago has brought about a new era of therapeutic progress and overall improvement in patient care, mainly due to the development and use of personalized medicine and tyrosine kinase inhibitors (TKIs). However, since the detection of BCR-ABL, BCR has been identified as a commonly occurring fusion partner in hematopoietic disorders. Read More

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Single nucleotide polymorphism in PTEN-Long gene: A risk factor in chronic myeloid leukemia.

Gene 2019 Apr 7;694:71-75. Epub 2019 Feb 7.

Laboratorio de Genética Hematológica, IMEX, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.

The BCR-ABL1 oncogene is associated with chronic myeloid leukemia (CML) pathogenesis, but the molecular mechanisms that initiate leukemogenesis are still unclear. Cancer pathogenesis has been associated with genetic alterations that may lead to inactivation of tumor suppressor genes. Phosphatase and tensin homolog (PTEN) is frequently deleted or inactivated in various tumors. Read More

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Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance.

EBioMedicine 2019 Mar 17;41:105-119. Epub 2019 Jan 17.

Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address:

Background: Alectinib has shown a greater efficacy to ALK-rearranged non-small-cell lung cancers in first-line setting; however, most patients relapse due to acquired resistance, such as secondary mutations in ALK including I1171N and G1202R. Although ceritinib or lorlatinib was shown to be effective to these resistant mutants, further resistance often emerges due to ALK-compound mutations in relapse patients following the use of ceritinib or lorlatinib. However, the drug for overcoming resistance has not been established yet. Read More

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The Association of rs2114358 in the miR-1206 Polymorphism to Chronic Myeloid Leukemia.

Microrna 2019 ;8(3):248-252

Department of Clinical Laboratory Science, College of Applied Medical Science, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Introduction: Association studies with factor candidates have advised that single nucleotide polymorphisms (SNPs) could also be related to CML progression and to the response to medical care. Genetic variation in miR-1206 of both derived and neighborhood SNPs process genes will contribute to the predisposition to cancer. The role of those with the risk of CML has not been extensively studied. Read More

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Predictive models for designing potent tyrosine kinase inhibitors in chronic myeloid leukemia for understanding its molecular mechanism of resistance by molecular docking and dynamics simulations.

J Biomol Struct Dyn 2019 11 22;37(18):4747-4766. Epub 2019 Feb 22.

Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre , Amrita Vishwa Vidyapeetham, Kochi Campus , Kerala State , India.

BCR-ABL fusion protein drives chronic myeloid leukemia (CML) which constitutively activates tyrosine kinase involved in the initiation and maintenance of CML phenotype. Ponatinib, an oral drug, was discovered as an efficient BCR-ABL inhibitor by addressing imatinib drug resistance arising due to the point mutations at its active sites. In this study, 44 BCR-ABL kinase inhibitors, which are derivatives of ponatinib, were used to develop a robust two-dimensional quantitative structure-activity relationship (2D-QSAR) and 3D-Pharmacophore models by dividing dataset into 32 training sets and 12 test set molecules. Read More

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November 2019

MISC: missing imputation for single-cell RNA sequencing data.

BMC Syst Biol 2018 12 14;12(Suppl 7):114. Epub 2018 Dec 14.

Joint Bioinformatics Program, University of Arkansas Little Rock George Washington Donaghey College of Engineering & IT and University of Arkansas for Medical Sciences, Little Rock, AR, 72204, USA.

Background: Single-cell RNA sequencing (scRNA-seq) technology provides an effective way to study cell heterogeneity. However, due to the low capture efficiency and stochastic gene expression, scRNA-seq data often contains a high percentage of missing values. It has been showed that the missing rate can reach approximately 30% even after noise reduction. Read More

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December 2018

Ganoderma tsugae induced ROS-independent apoptosis and cytoprotective autophagy in human chronic myeloid leukemia cells.

Food Chem Toxicol 2019 Feb 19;124:30-44. Epub 2018 Nov 19.

Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, 40402, Taiwan. Electronic address:

The medicinal fungus Ganoderma, known in Chinese as Lingzhi or Reishi, traditionally has various medicinal uses and has been employed in cancer treatment in Asia for centuries. This study used ethanol-extracted Ganoderma tsugae (GT) and examined its antitumor activities on human chronic myeloid leukemia cells as well as its molecular mechanism of action. Treatment with GT (200-400 μg/mL) significantly reduced cell viability and caused G2/M arrest in K562 cells. Read More

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February 2019

Discovery of (E)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)propanamide (CHMFL-ABL-121) as a highly potent ABL kinase inhibitor capable of overcoming a variety of ABL mutants including T315I for chronic myeloid leukemia.

Eur J Med Chem 2018 Dec 5;160:61-81. Epub 2018 Oct 5.

High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, PR China; Precision Medicine Research Laboratory of Anhui Province, Hefei, Anhui, 230088, PR China. Electronic address:

There is still a great demand in the clinic for the drugs which can overcome a variety of imatinib resistant ABL mutants. Starting from a type I inhibitor axitinib, which has been reported to overcome ABL-T315I mutant induced resistance, through a structure guided drug design approach and binding mode switch strategy, we have discovered a novel type II ABL inhibitor 24 (CHMFL-ABL-121), which significantly improved the inhibitory activity against ABL wt and a broad spectrum of mutants including the most prevalent imatinib-resistant gatekeeper mutant T315I. 24 exhibited IC values of 2 nM and 0. Read More

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December 2018

Ponatinib in the treatment of chronic myeloid leukemia and philadelphia chromosome positive acute lymphoblastic leukemia.

Future Oncol 2019 Jan 25;15(3):257-269. Epub 2018 Sep 25.

Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL, USA.

Philadelphia chromosome, reciprocal translocation between chromosome 9 and 22, leading to a constitutively active fusion protein BCR-ABL1 is the common feature among Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML). The discovery of tyrosine kinase inhibitors (TKIs) has led to significant improvement in the treatment of CML and Ph+ ALL. Ponatinib is a third-generation TKI that is currently approved as per label when no other TKIs are indicated for the treatment of patients with CML and Ph+ ALL after failing treatment with second-generation TKIs or if presence of T315I mutation is discovered. Read More

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January 2019

Identification of Prognostic and Susceptibility Markers in Chronic Myeloid Leukemia Using Next Generation Sequencing.

Ethiop J Health Sci 2018 Mar;28(2):135-146

Department of Medical Oncology, Sir Ganga Ram Hospital, Rajinder Nagar, Delhi, India.

Background: Incidence of Chronic Myeloid Leukemia (CML) is continuously increasing and expected to reach 100,000 patients every year by 2030. Though the discovery of Imatinib Mesylate (IM) has brought a paradigm shift in CML treatment, 20% patients show resistance to this tyrosine kinase inhibiter (TKI). Therefore, it is important to identify markers, which can predict the occurrence and prognosis of CML. Read More

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Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy.

J Hematol Oncol 2018 06 20;11(1):84. Epub 2018 Jun 20.

Department of Clinical and Experimental Medicine, Section of Hematology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.

Bcr-Abl inhibitors paved the way of targeted therapy epoch. Imatinib was the first tyrosine kinase inhibitor to be discovered with high specificity for Bcr-Abl protein resulting from t(9, 22)-derived Philadelphia chromosome. Although the specific targeting of that oncoprotein, several Bcr-Abl-dependent and Bcr-Abl-independent mechanisms of resistance to imatinib arose after becoming first-line therapy in chronic myelogenous leukemia (CML) treatment. Read More

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