Individualizing kinase-targeted cancer therapy: the paradigm of chronic myeloid leukemia

The success of tyrosine kinase inhibitors in treating chronic myeloid leukemia highlights the potential of targeting oncogenic kinases with small molecules. By using drug activity profiles and individual patient genotypes, one can guide personalized therapy selection for patients with resistance.

• Publication year

  2014

• Venue

  Genome Biology

• Publication date

  2014-09-17

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s13059-014-0461-8PMID 25316524PMCID 4318205
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Combined STAT3 and BCR-ABL1 inhibition induces synthetic lethality in therapy-resistant chronic myeloid leukemia

  2017cited by this paper
• Functional heterogeneity of genetically defined subclones in acute myeloid leukemia.

  2014cited by this paper
• The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer.

  2014cited by this paper
• Molecular dynamics reveal BCR-ABL1 polymutants as a unique mechanism of resistance to PAN-BCR-ABL1 kinase inhibitor therapy

  2014cited by this paper
• Ceritinib in ALK-rearranged non-small-cell lung cancer.

  2014cited by this paper
• Ceritinib in ALK-rearranged non-small-cell lung cancer.

  2014cited by this paper
• Many BCR-ABL1 compound mutations reported in chronic myeloid leukemia patients may actually be artifacts due to PCR-mediated recombination.

  2014cited by this paper
• MDR1 expression predicts outcome of Ph+ chronic phase CML patients on second-line nilotinib therapy after imatinib failure

  2014cited by this paper
• Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib.

  2014cited by this paper
• Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib.

  2014cited by this paper
• BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia.

  2014cited by this paper
• Combined STAT3 and BCR-ABL1 Inhibition Induces Synthetic Lethality in Therapy-Resistant Chronic Myeloid Leukemia

  2014cited by this paper
• BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML: frequency and clonal relationships.

  2013cited by this paper
• Tumor adaptation and resistance to RAF inhibitors

  2013cited by this paper
• Cancer-drug discovery and cardiovascular surveillance.

  2013cited by this paper
• Investigational Janus kinase inhibitors

  2013cited by this paper
• Long-term follow-up of treatment with imatinib in eosinophilia-associated myeloid/lymphoid neoplasms with PDGFR rearrangements in blast phase

  2013cited by this paper
• PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells.

  2013cited by this paper
• European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013.

  2013cited by this paper
• Unraveling the complexity of tyrosine kinase inhibitor-resistant populations by ultra-deep sequencing of the BCR-ABL kinase domain.

  2013cited by this paper
• Unraveling a novel transcription factor code determining the human arterial-specific endothelial cell signature.

  2013cited by this paper
• Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I

  2013cited by this paper
• Genetic and epigenetic alterations of myeloproliferative disorders

  2013cited by this paper
• Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I

  2013cited by this paper
• The quantitative level of T315I mutated BCR-ABL predicts for major molecular response to second-line nilotinib or dasatinib treatment in patients with chronic myeloid leukemia

  2013cited by this paper
• Kinase pathway dependence in primary human leukemias determined by rapid inhibitor screening.

  2013cited by this paper
• Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

  2013cited by this paper
• A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias.

  2013influential reference
• Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.

  2013cited by this paper
• An Unbiased shRNA Library Screen Identifies Nucleocytoplasmic Transport As a Potential Target For Treatment Of Chronic Myeloid Leukemia

  2013cited by this paper
• Somatic mutations of calreticulin in myeloproliferative neoplasms.

  2013cited by this paper
• Ibrutinib in relapsed chronic lymphocytic leukemia.

  2013cited by this paper
• Direct Contact With Bone Marrow Stromal Cells Protects CML Progenitors From Imatinib Through Cytoplasmic Stabilization Of β-Catenin

  2013cited by this paper
• Ibrutinib in relapsed chronic lymphocytic leukemia.

  2013influential reference
• Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia

  2012cited by this paper
• Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION).

  2012cited by this paper
• The origin and evolution of mutations in acute myeloid leukemia.

  2012cited by this paper
• Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial.

  2012cited by this paper
• Structural and Spectroscopic Analysis of the Kinase Inhibitor Bosutinib and an Isomer of Bosutinib Binding to the Abl Tyrosine Kinase Domain

  2012cited by this paper
• Three novel patient‐derived BCR/ABL mutants show different sensitivity to second and third generation tyrosine kinase inhibitors

  2012cited by this paper
• Poor response to second-line kinase inhibitors in chronic myeloid leukemia patients with multiple low-level mutations, irrespective of their resistance profile.

  2012cited by this paper
• A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer

  2012cited by this paper
• BRAF inhibition in refractory hairy-cell leukemia.

  2012cited by this paper
• A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis.

  2012cited by this paper
• Microenvironmental protection of CML stem and progenitor cells from tyrosine kinase inhibitors through N-cadherin and Wnt-β-catenin signaling.

  2012cited by this paper
• Pushing the limits of targeted therapy in chronic myeloid leukaemia

  2012cited by this paper
• Mechanisms of Acquired Crizotinib Resistance in ALK-Rearranged Lung Cancers

  2012cited by this paper
• Blockade of JAK2-mediated extrinsic survival signals restores sensitivity of CML cells to ABL inhibitors

  2012cited by this paper
• A deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations in 76.9% of cases

  2011cited by this paper
• BCR-ABL1-independent PI3Kinase activation causing imatinib-resistance

  2011cited by this paper
• Improved survival with vemurafenib in melanoma with BRAF V600E mutation.

  2011cited by this paper
• Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-α in newly diagnosed chronic myeloid leukemia.

  2011cited by this paper
• Quantitative phosphoproteomics revealed interplay between Syk and Lyn in the resistance to nilotinib in chronic myeloid leukemia cells.

  2011cited by this paper
• High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia.

  2011cited by this paper
• BRAF mutations in hairy-cell leukemia.

  2011cited by this paper
• Gastrointestinal stromal tumours: origin and molecular oncology

  2011cited by this paper
• Sensitive detection of BCR-ABL1 mutations in patients with chronic myeloid leukemia after imatinib resistance is predictive of outcome during subsequent therapy.

  2011cited by this paper
• Protein kinase signaling networks in cancer.

  2011cited by this paper
• SHP-1 expression accounts for resistance to imatinib treatment in Philadelphia chromosome-positive cells derived from patients with chronic myeloid leukemia.

  2011cited by this paper
• The regulatory crosstalk between kinases and proteases in cancer

  2010cited by this paper
• Chronic myeloid leukemia: mechanisms of blastic transformation.

  2010cited by this paper
• Functional activity of the OCT-1 protein is predictive of long-term outcome in patients with chronic-phase chronic myeloid leukemia treated with imatinib.

  2010cited by this paper
• Personalized medicine and inhibition of EGFR signaling in lung cancer.

  2009cited by this paper
• AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance.

  2009cited by this paper
• Genetic Variations Associated with Overall and Progression-Free Survival in Multiple Myeloma Patients Treated with Thalidomide Combinations

  2009cited by this paper
• International randomized study of interferon Vs STI571 (IRIS) 8-year follow up: Sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib

  2009cited by this paper
• Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia

  2008cited by this paper
• BCR–ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros

  2008cited by this paper
• BCR-ABL mutants spread resistance to non-mutated cells through a paracrine mechanism

  2008cited by this paper
• Failure of CDKN2A/B (INK4A/B-ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL.

  2008cited by this paper
• Solution Conformations and Dynamics of ABL Kinase-Inhibitor Complexes Determined by NMR Substantiate the Different Binding Modes of Imatinib/Nilotinib and Dasatinib*♦

  2008cited by this paper
• Dynamics of BCR-ABL mutated clones prior to hematologic or cytogenetic resistance to imatinib

  2008cited by this paper
• Cryptic and partial deletions of PRDM16 and RUNX1 without t(1;21)(p36;q22) and/or RUNX1–PRDM16 fusion in a case of progressive chronic myeloid leukemia: A complex chromosomal rearrangement of underestimated frequency in disease progression?

  2008cited by this paper
• Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency.

  2007cited by this paper
• Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias.

  2006influential reference
• Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL.

  2006influential reference
• Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia.

  2006cited by this paper
• Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants

  2006cited by this paper
• Kinase Domain Mutants of Bcr-Abl Exhibit Altered Transformation Potency, Kinase Activity, and Substrate Utilization, Irrespective of Sensitivity to Imatinib

  2006cited by this paper
• MPLW515L Is a Novel Somatic Activating Mutation in Myelofibrosis with Myeloid Metaplasia

  2006cited by this paper
• OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib.

  2006cited by this paper
• A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera

  2005cited by this paper
• Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain

  2005cited by this paper
• A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.

  2005cited by this paper
• High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy.

  2005cited by this paper
• Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl.

  2005cited by this paper
• Anticancer drugs: To the rescue?

  2004cited by this paper
• Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.

  2004cited by this paper
• A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome.

  2003cited by this paper
• Cooperation of BCR-ABL and AML1/MDS1/EVI1 in blocking myeloid differentiation and rapid induction of an acute myelogenous leukemia

  2001cited by this paper
• Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification

  2001cited by this paper
• Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.

  2000cited by this paper
• Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia

  1996cited by this paper
• Homozygous deletions of the p16 tumor-suppressor gene are associated with lymphoid transformation of chronic myeloid leukemia.

  1995cited by this paper
• p53 in chronic myelogenous leukemia in acute phase.

  1991cited by this paper
• Correlation between chromosomal abnormalities and blast phenotype in the blast crisis of Ph-positive CGL.

  1986influential reference
• [Double Philadelphia chromosome and isochromosome 17 in the terminal phase of chronic myeloid leukemia].

  1966cited by this paper
• Doppel-Philadelphia-Chromosom und Isochromosom 17 in der terminalen Phase der chronischen myeloischen Leukämie

  1966cited by this paper

• Results of asciminib therapy as part of managed access program in patients with chronic myeloid leukemia with T315I mutation

  2025cites this paper
• Potential signaling pathways, biomarkers, natural drugs, and chronic myeloid leukemia therapeutics

  2025cites this paper
• Comprehensive resistance profiling of chronic myeloid leukaemia associated ABL1 variants against five tyrosine kinase inhibitors using prime editing.

  2025cites this paper
• Molecular biomarkers of leukemia: convergence-based drug resistance mechanisms in chronic myeloid leukemia and myeloproliferative neoplasms

  2024cites this paper
• Exploring treatment decision-making in chronic myeloid leukemia in chronic phase

  2024cites this paper
• Exploring Inhibition Mechanisms in Wildtype and T315I BCR‐ABL1: An In Silico Approach Integrating Virtual Screening, MD Simulations, and MM‐GBSA Analysis

  2024cites this paper
• Ponatinib in the treatment of patients with chronic myeloid leukemia and increased cardiovascular risk: A review of management strategies

  2024cites this paper
• Ponatinib‐review of historical development, current status, and future research

  2024cites this paper
• Tyrosine kinase inhibitor response of ABL-class acute lymphoblastic leukemia: the role of kinase type and SH3 domain

  2024cites this paper
• Clonal evolution in tyrosine kinase inhibitor-resistance: lessons from in vitro-models

  2023cites this paper
• Molecular Mechanisms of Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.

  2023cites this paper
• Development of Asciminib, a Novel Allosteric Inhibitor of BCR-ABL1.

  2022cites this paper
• Pharmacogenomics of Impaired Tyrosine Kinase Inhibitor Response: Lessons Learned From Chronic Myelogenous Leukemia

  2021cites this paper
• A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity

  2020cites this paper
• Multiple Molecular Mechanisms Contribute Towards In Vitro Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukaemia

  2019cites this paper
• Genetics and tyrosine kinase inhibitors of chronic myeloid leukemia

  2019influential citation
• Acquisition of Inv(16)(p13q22) in a blast crisis of chronic myeloid leukemia: case report

  2019cites this paper
• Acquisition of Inv(16)(p13q22) in a blast crisis of chronic myeloid leukemia: case report.

  2019cites this paper
• Mutations Associated with Imatinib Mesylate Resistance - Review

  2018cites this paper
• HeberFERON, a new formulation of IFNs with improved pharmacodynamics: Perspective for cancer treatment.

  2018cites this paper
• Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy

  2018cites this paper
• MLF1 protein is a potential therapy target for lung adenocarcinoma.

  2018cites this paper
• Patients in Focus: What’s Relevant for Chronic Myeloid Leukaemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukaemia?

  2017cites this paper
• First‐line treatment selection and early monitoring patterns in chronic phase‐chronic myeloid leukemia in routine clinical practice: SIMPLICITY

  2017cites this paper
• T315I+ tyrosine-kinase independent CML cells resistance

  2017cites this paper
• The development of agents targeting the BCR-ABL tyrosine kinase as Philadelphia chromosome-positive acute lymphoblastic leukemia treatment

  2016cites this paper
• Chronic myeloid leukemia: reminiscences and dreams

  2016cites this paper
• Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: An Evolving Paradigm of Molecularly Targeted Therapy

  2016cites this paper
• Molecular monitoring in CML and the prospects for treatment-free remissions.

  2015cites this paper
• Diagnosing and managing advanced chronic myeloid leukemia.

  2015cites this paper
• Chronic Myeloid Leukemia: Advances in Understanding Disease Biology and Mechanisms of Resistance to Tyrosine Kinase Inhibitors

  2015influential citation
• Individualized chemical systems medicine of acute and chronic myeloid leukemia

  2015cites this paper
• Tumor heterogeneity: next-generation sequencing enhances the view from the pathologist’s microscope

  2014cites this paper