Affinage

BCR

Breakpoint cluster region protein · UniProt P11274

Length
1271 aa
Mass
142.8 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCR encodes a ubiquitously expressed 160-kDa cytosolic phosphoprotein of 1271 amino acids that carries an intrinsic serine/threonine kinase activity (PMID:3299055, PMID:3285291, PMID:2232885). Its principal biomedical importance derives from the Philadelphia translocation, which fuses 5' BCR sequences (the first ~902–927 residues) to the 3' ABL oncogene to create the chimeric BCR-ABL mRNA and fusion oncoprotein that is the essential molecular event in chronic myeloid leukemia (PMID:3332859, PMID:3859408, PMID:3285291). Within the fusion, the BCR moiety supplies an N-terminal coiled-coil domain that drives oligomerization and tetramerization of BCR-ABL, constitutively activating the ABL tyrosine kinase and enabling membrane clustering and downstream MAPK signaling (PMID:12476302, PMID:36369657). Reciprocally, normal BCR is a negative regulator of ABL: it forms a complex with c-Abl and, through phosphoserine-354, binds the ABL SH2 domain to inhibit kinase activity, while BCR-ABL-mediated tyrosine autophosphorylation inactivates BCR's own serine/threonine kinase (PMID:12476302, PMID:12543778). The oncogenic kinase rewires hematopoietic cells, driving growth-factor-independent S-phase entry (PMID:9488616) and signaling through STAT5 to sustain anti-apoptotic and proliferative targets including Bcl-x, Mcl-1, c-Myc and cyclin D2 (PMID:12483533), through PI3K (with PTEN downregulation in leukemic stem cells) (PMID:16849647, PMID:19965668), and through partner complexes with CBL, CRKL, AHI-1 and JAK2 (PMID:9195915, PMID:18936234). Downstream transcriptional reprogramming includes PRAME/EZH2-mediated TRAIL suppression, IRF5 tyrosine phosphorylation and inactivation, and THAP11 suppression that upregulates c-Myc (PMID:24445143, PMID:20838376, PMID:21400515). BCR-ABL expression is itself driven by MYC/MAX binding to the BCR promoter (PMID:26179066), and the oncoprotein is subject to K63-linked ubiquitination and aggresomal sequestration as well as targeted degradation strategies that abolish its signaling (PMID:21248063, PMID:37392851).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1987 High

    Established that the normal BCR gene product is an enzyme, defining it as a 160-kDa phosphoprotein with intrinsic serine/threonine kinase activity rather than a passive structural protein.

    Evidence Protein expression analysis and in vitro kinase assay in leukemic cells

    PMID:3299055

    Open questions at the time
    • Physiological substrates of BCR's own kinase not identified
    • Regulation of BCR kinase activity in normal cells unknown
  2. 1987 High

    Defined the molecular basis of CML by showing BCR is fused head-to-tail to ABL by the Philadelphia translocation, generating a chimeric mRNA and fusion protein.

    Evidence Molecular cloning, Southern blot and chimeric mRNA characterization

    PMID:3332859 PMID:3859408

    Open questions at the time
    • Mechanism by which fusion activates ABL not yet defined at this stage
    • Functional consequence of the BCR portion unresolved
  3. 1988 High

    Provided the full protein coding sequence (1271 aa) and showed BCR is broadly expressed, while delimiting the BCR segment (first ~902–927 aa) retained in BCR-ABL.

    Evidence cDNA cloning, Northern blot and sequence analysis

    PMID:3285291

    Open questions at the time
    • Domain function within the retained BCR segment not yet assigned
  4. 1985 High

    Showed BCR-ABL fusion is the essential molecular lesion in CML even when the Philadelphia chromosome is cytogenetically invisible, establishing the fusion (not the visible chromosome) as the disease driver.

    Evidence Southern blot and molecular rearrangement analysis in Ph1-negative CML

    PMID:3859408

    Open questions at the time
    • Does not address how the fusion transforms cells mechanistically
  5. 1990 High

    Localized both normal BCR and p210 BCR-ABL to the cytosol, framing where the kinase activity is deployed.

    Evidence Subcellular fractionation with in vivo radiolabeling and immunoprecipitation

    PMID:2232885

    Open questions at the time
    • Did not address dynamic or signal-induced membrane recruitment
  6. 1987 High

    Demonstrated that membrane targeting is rate-limiting for fibroblast transformation, since p210 BCR-ABL fails to transform NIH/3T3 cells but a myristylated gag-BCR-ABL does.

    Evidence NIH/3T3 transformation assay with defined retroviral BCR-ABL constructs

    PMID:2440107

    Open questions at the time
    • Relevance of fibroblast assay to hematopoietic transformation unclear
    • Did not define the activating role of BCR coiled-coil oligomerization
  7. 2002 Medium

    Resolved the reciprocal regulatory relationship: the BCR coiled-coil drives tetramerization that activates ABL, while phosphoserine-354 BCR binds the ABL SH2 domain to inhibit the oncogenic kinase.

    Evidence Biochemical and kinase assays, Co-IP, and serine 354 mutagenesis

    PMID:12476302

    Open questions at the time
    • Single-lab biochemistry without structural confirmation at this stage
    • Stoichiometry and dynamics of activation versus inhibition not quantified
  8. 2003 Medium

    Established normal Bcr as a major endogenous inhibitor of cytoplasmic c-Abl, with Abl SH2 sequestering Bcr to release c-Abl from inhibition.

    Evidence Co-IP, kinase and transformation assays, overexpression in hematopoietic and insect cells

    PMID:12543778

    Open questions at the time
    • Physiological context where this regulation operates unclear
    • Single-lab evidence
  9. 2023 Medium

    Defined the structural logic of BCR coiled-coil assembly, identifying a binary unit and α1-helix aromatic packing that builds the tetramer required for membrane clustering and MAPK signaling.

    Evidence Molecular dynamics simulations with crystallographic validation and structural analysis

    PMID:36369657

    Open questions at the time
    • Primary contribution is computational modeling
    • Direct functional test of individual packing residues in cells limited
  10. 1997 Medium

    Mapped CBL recruitment to the BCR-ABL SH2 domain (phospho-dependent) and identified CRKL as a bridging adapter, building the BCR-ABL adaptor complex.

    Evidence Co-IP, domain deletion mapping and pulldown assays

    PMID:9195915

    Open questions at the time
    • Secondary CBL interaction site not identified
    • Functional output of the complex not measured here
  11. 1998 Medium

    Showed BCR-ABL kinase activity, not mere expression, drives growth-factor-independent S-phase entry, confirming kinase function as the proliferative driver.

    Evidence Cell cycle flow cytometry with ABL inhibitor CGP 57148 in primary CML cells

    PMID:9488616

    Open questions at the time
    • Downstream effectors linking kinase to cell-cycle machinery not defined here
  12. 2002 Medium

    Connected BCR-ABL kinase to constitutive STAT5 activation and identified anti-apoptotic/proliferative STAT5 targets, defining a core survival pathway.

    Evidence Kinase inhibitor and dominant-negative Stat5 expression, EMSA, apoptosis assays in K562

    PMID:12483533

    Open questions at the time
    • Direct versus indirect regulation of named targets not fully separated
    • Single-lab data
  13. 2002 High

    Demonstrated genetic cooperation between BCR-ABL and NUP98/HOXA9 in driving blast crisis while preserving BCR-ABL kinase dependence.

    Evidence Murine bone marrow transplantation with genetic epistasis and STI571 treatment

    PMID:12032333

    Open questions at the time
    • Molecular mechanism of cooperation between the two oncogenes not resolved
  14. 2006 Medium

    Identified a PI3K-dependent BCR-ABL output driving histidine decarboxylase expression and histamine synthesis in basophilic CML cells.

    Evidence BCR-ABL expression in Ba/F3, PI3K inhibition, RT-PCR, histamine measurement, TKI treatment

    PMID:16849647

    Open questions at the time
    • Transcription factors linking PI3K to HDC not defined
    • Single-lab evidence
  15. 2008 High

    Identified AHI-1 as a scaffold forming an AHI-1–BCR-ABL–JAK2 complex that sustains BCR-ABL/JAK2-STAT5 phosphorylation and growth autonomy of CML stem/progenitor cells.

    Evidence Reciprocal Co-IP, RNAi, overexpression, colony assays and in vivo leukemia model

    PMID:18936234

    Open questions at the time
    • Structural basis of the ternary complex unknown
    • Whether AHI-1 acts on normal BCR not addressed
  16. 2009 High

    Placed BCR-ABL upstream of PTEN downregulation in leukemic stem cells, with PTEN acting via Akt1 to restrain leukemogenesis.

    Evidence Murine BCR-ABL leukemia model with conditional Pten deletion/overexpression and stem cell assays

    PMID:19965668

    Open questions at the time
    • Mechanism by which BCR-ABL represses PTEN not defined
  17. 2010 Low

    Suggested BCR and BCR/ABL1 share a common transcriptional control that is downregulated during normal myeloid differentiation but deregulated in trans in blast crisis.

    Evidence Gene expression analysis across myeloid differentiation and CML phases

    PMID:20520635

    Open questions at the time
    • No direct promoter or transcription factor binding experiments
    • Correlative expression data only
    • Single lab
  18. 2010 Medium

    Defined a BCR-ABL–PRAME–EZH2 axis that epigenetically suppresses TRAIL, linking the oncogene to apoptosis resistance.

    Evidence RNAi of PRAME/EZH2, ChIP of EZH2 on TRAIL promoter, RT-PCR/Western

    PMID:20838376

    Open questions at the time
    • Mechanism of PRAME upregulation by BCR-ABL unresolved
  19. 2011 Medium

    Showed K63-linked ubiquitination (via Usp9x inhibition) drives BCR-ABL into aggresomes where it cannot signal, identifying a degradative vulnerability independent of imatinib resistance status.

    Evidence Ubiquitin linkage and aggresome analysis, signaling and apoptosis assays with WP1130

    PMID:21248063

    Open questions at the time
    • Endogenous E3 ligase mediating K63 modification not identified
    • Single-lab evidence
  20. 2011 Medium

    Established that BCR-ABL kinase suppresses THAP11 to relieve repression of c-Myc, driving proliferation via c-Myc/cyclin D1/ODC and reduced p21.

    Evidence Abl inhibitor, BCR-ABL siRNA, THAP11 overexpression, colony assays, RT-PCR/Western

    PMID:21400515

    Open questions at the time
    • How kinase activity represses THAP11 not defined
    • Single-lab evidence
  21. 2014 Medium

    Showed BCR-ABL interacts with and tyrosine-phosphorylates IRF5 to reduce its transcriptional activity, with a Y104F mutant implying additional phosphosites.

    Evidence Co-IP, phosphorylation analysis, Y104F mutagenesis, transcription assays, imatinib treatment

    PMID:24445143

    Open questions at the time
    • Additional phosphorylation sites not mapped
    • Functional consequence of IRF5 inactivation in CML pathology incompletely defined
  22. 2015 High

    Identified MYC/MAX as direct transcriptional drivers of BCR and BCR/ABL1 via promoter binding, creating a feed-forward loop with c-Myc as both upstream and downstream of the oncogene.

    Evidence ChIP, MYC overexpression/silencing, luciferase reporter, Western blot

    PMID:26179066

    Open questions at the time
    • Interplay with the proposed differentiation-linked control not integrated
  23. 2023 Medium

    Demonstrated that BCR-ABL can be selectively eliminated via N-end rule ubiquitin-proteasome PROTACs, providing a tunable degradation strategy with in vivo efficacy.

    Evidence Single amino acid PROTACs with N-end rule mutagenesis, proliferation assays, K562 xenograft

    PMID:37392851

    Open questions at the time
    • Selectivity over normal BCR not fully established
    • Single-lab proof of concept

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological function and substrates of normal BCR's serine/threonine kinase, and how its inhibitory regulation of c-Abl operates in healthy cells, remain undefined relative to the well-characterized oncogenic fusion.
  • No physiological BCR kinase substrate identified
  • Normal cellular role of BCR distinct from its fusion partner role unclear
  • Structure of full-length BCR not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0016740 transferase activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2
Partners
ABL1AHI1CBLCRKLIRF5JAK2

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 The normal BCR gene encodes a 160,000-dalton phosphoprotein (designated PHL) with associated serine/threonine kinase activity, as demonstrated by expression studies and kinase assays in leukemic cells. Protein expression analysis and in vitro kinase assay Molecular and cellular biology High 3299055
1987 The BCR gene on chromosome 22 is fused in a head-to-tail fashion to the ABL oncogene as a consequence of the Philadelphia translocation, generating a chimeric BCR/ABL mRNA with 5' BCR and 3' ABL sequences that encodes an abnormal fusion protein. Molecular cloning, Southern blot, chimeric mRNA characterization Bailliere's clinical haematology High 3332859 3859408
1988 The BCR gene encodes a protein of 1271 amino acids; its transcripts (7.0 and 4.5 kb) are expressed in all cell types examined, and the first 902–927 amino acids of BCR are included within the CML-specific BCR-ABL chimeric mRNA. cDNA cloning, Northern blot, sequence analysis Oncogene High 3285291
1990 Both normal BCR protein products and the p210 BCR-ABL fusion protein are recovered predominantly from the cytosolic fraction, not the membrane fraction, as shown by subcellular fractionation and in vivo labeling experiments. Subcellular fractionation, in vivo radiolabeling, immunoprecipitation Leukemia High 2232885
1987 The P210 BCR-ABL protein does not transform NIH/3T3 fibroblasts (unlike v-abl), but a gag-BCR-ABL recombinant that adds myristylation-dependent membrane localization does transform fibroblasts, indicating that a membrane-targeting signal is required for fibroblast transformation by BCR-ABL. NIH/3T3 transformation assay, retroviral expression of BCR-ABL cDNA constructs Science High 2440107
1985 BCR rearrangement and joint translocation of BCR and c-ABL sequences occur even in Ph1-negative CML patients, demonstrating that BCR-ABL fusion is the essential molecular event in CML regardless of Philadelphia chromosome visibility. Southern blot, molecular analysis of chromosomal rearrangements The EMBO journal High 3859408
2002 BCR acts as a negative regulator of the BCR-ABL oncoprotein: the BCR coiled-coil domain at its amino-terminus drives oligomerization (tetramerization) of BCR-ABL, which activates ABL tyrosine kinase. BCR-ABL autophosphorylation on tyrosines inactivates the serine/threonine kinase activity of BCR. Phosphoserine-BCR binds to the ABL SH2 domain and inhibits BCR-ABL tyrosine kinase; serine 354 of BCR is critical for this inhibition. Biochemical assays, mutagenesis (serine 354), co-immunoprecipitation, kinase assays Oncogene Medium 12476302
2003 Bcr is a major inhibitor of cytoplasmic c-Abl: endogenous Bcr forms a complex with c-Abl in hematopoietic and insect cells, and overexpression of Bcr suppresses activated c-Abl tyrosine kinase activity and reverses oncogenic transformation induced by an Abl SH2 construct. Bcr and the Abl SH2 protein were found in a complex, and sequestration of Bcr by Abl SH2 releases c-Abl from inhibition. Co-immunoprecipitation, kinase assays, cell transformation assays, overexpression studies Cancer research Medium 12543778
2023 The BCR coiled-coil (CC) domain at the N-terminus controls BCR-ABL oligomerization. Molecular dynamics simulations combined with crystallography validation showed that a binary complex of the BCR CC domain serves as the basic unit; the small α1-helix forms interchain aromatic dimeric packing in binary assembly and contributes to dimer-dimer packing in the quaternary assembly, driving tetramerization essential for membrane clustering and MAPK signaling. Molecular dynamics simulations, crystallography (literature-validated), structural analysis Protein science Medium 36369657
1997 c-CBL binds directly to the SH2 domain of BCR-ABL only when c-CBL is tyrosine-phosphorylated; however, deletion of the SH2 domain did not fully abolish CBL-BCR-ABL complex formation, suggesting a secondary interaction site or indirect bridging via CRKL. CRKL (an SH2/SH3 adapter) can mediate complex formation between c-CBL and BCR-ABL. Co-immunoprecipitation, domain deletion mapping, pulldown assays The Journal of biological chemistry Medium 9195915
2002 BCR-ABL kinase activity (but not expression alone) is required for constitutive entry of primary myeloid CML cells into S phase independent of growth factors; the defect in growth factor-dependent cell cycle arrest is completely corrected by the ABL-specific inhibitor CGP 57148. Cell cycle analysis (flow cytometry), kinase inhibitor treatment, primary CML cell culture British journal of haematology Medium 9488616
2002 BCR-ABL cooperates with NUP98/HOXA9 to cause blast crisis in a murine bone marrow transplantation model; the blast crisis phenotype depends on both BCR-ABL and NUP98/HOXA9 expression. Blast crisis tumors retain sensitivity to the ABL inhibitor STI571 in vitro and in vivo, confirming continued BCR-ABL kinase dependence. Murine bone marrow transplantation model, genetic epistasis, in vitro/in vivo STI571 treatment PNAS High 12032333
2002 Bcr-Abl kinase inhibition by PD180970 blocks constitutive Stat5 DNA-binding activity and suppresses CML cell proliferation/induces apoptosis; dominant-negative Stat5 alone also induces apoptosis in K562 cells. Candidate Stat5 target genes including Bcl-x, Mcl-1, c-Myc, and cyclin D2 are downregulated after BCR-ABL kinase inhibition. Kinase inhibitor treatment, dominant-negative Stat5 expression via vaccinia virus vector, EMSA, Western blot, apoptosis assay Oncogene Medium 12483533
2008 AHI-1 interacts with BCR-ABL and JAK2 to form an AHI-1–BCR-ABL–JAK2 protein complex in CML cells. Overexpression of AHI-1 sustains BCR-ABL and JAK2-STAT5 phosphorylation and reverses growth deficiencies from BCR-ABL down-regulation; RNAi suppression of AHI-1 reduces growth autonomy of CML stem/progenitor cells. Co-immunoprecipitation, RNAi knockdown, phosphorylation analysis, in vitro colony assays, in vivo leukemia model Journal of Experimental Medicine High 18936234
2011 BCR-ABL is rapidly modified with K63-linked ubiquitin polymers upon treatment with the ubiquitin-cycle inhibitor WP1130 (which directly inhibits the deubiquitinase Usp9x), leading to BCR-ABL accumulation in aggresomes where it cannot conduct signal transduction, and inducing apoptosis in both imatinib-sensitive and -resistant CML cells. Ubiquitin linkage analysis, aggresome detection, kinase signaling assays, apoptosis assay, Usp9x deubiquitinase activity assay Blood Medium 21248063
2015 MYC and its partner MAX bind to the BCR promoter (demonstrated by ChIP) and upregulate BCR and BCR/ABL1 at both transcriptional and protein levels; silencing MYC in BCR/ABL1-positive cell lines significantly downregulates BCR and BCR/ABL1 expression, decreasing proliferation and inducing cell death. Chromatin immunoprecipitation (ChIP), MYC overexpression/silencing, luciferase reporter assay, Western blot Molecular cancer High 26179066
2010 BCR and BCR/ABL1 are similarly downregulated during myeloid differentiation in healthy donors and in chronic-phase CML patients but not in blast crisis, suggesting BCR and BCR/ABL1 share a common transcriptional control mechanism that is disrupted in blast crisis (in trans deregulation of both BCR and BCR/ABL1 promoters). Gene expression analysis during myeloid differentiation, comparison across CML phases Leukemia Low 20520635
2006 BCR-ABL promotes expression of histidine decarboxylase (HDC) and synthesis of histamine in CML basophilic cells via the PI3-kinase signaling pathway; BCR-ABL tyrosine kinase inhibitors (imatinib, nilotinib) decreased HDC mRNA expression and histamine levels in BCR-ABL-transformed cells and primary CML cells. BCR-ABL expression in Ba/F3 cells, PI3K pathway inhibition, RT-PCR, histamine measurement, TKI treatment Blood Medium 16849647
2014 IRF5 is expressed in CML cells where it interacts with BCR-ABL kinase, which induces IRF5 tyrosine phosphorylation and reduces its transcriptional activity; imatinib partially restores IRF5 transcriptional activity. A BCR-ABL consensus site mutant (IRF5 Y104F) still shows tyrosine phosphorylation, suggesting additional phosphorylation sites or downstream kinase involvement. Co-immunoprecipitation, phosphorylation analysis, site-directed mutagenesis (Y104F), transcriptional activity assay, imatinib treatment Carcinogenesis Medium 24445143
2010 BCR-ABL-mediated upregulation of PRAME leads to increased EZH2 binding to the TRAIL promoter and suppression of TRAIL expression in CML cells; knockdown of PRAME or EZH2 by RNA interference restores TRAIL expression and enhances imatinib sensitivity. RNAi knockdown of PRAME and EZH2, chromatin immunoprecipitation (EZH2 on TRAIL promoter), RT-PCR, Western blot Oncogene Medium 20838376
2009 PTEN is downregulated by BCR-ABL in leukemia stem cells in CML; PTEN deletion accelerates CML development while PTEN overexpression delays CML and B-ALL development, suppresses leukemia stem cells, and induces cell-cycle arrest. PTEN suppresses B-ALL through regulating its downstream gene Akt1. Mouse model of BCR-ABL-induced leukemia, conditional Pten deletion, PTEN overexpression, stem cell assays, cell-cycle analysis Blood High 19965668
2011 BCR-ABL kinase activity suppresses expression of Thanatos-associated protein 11 (THAP11) in CML cells; THAP11 inhibits c-Myc transcription and its restoration by Abl kinase inhibitors reduces c-Myc expression, cyclin D1, ODC, and increases p21Cip1, inhibiting CML cell proliferation. Abl kinase inhibitor treatment, siRNA depletion of BCR-ABL, THAP11 overexpression, colony forming assay, RT-PCR, Western blot International journal of cancer Medium 21400515
2023 BCR-ABL protein can be selectively degraded via the N-end rule ubiquitin-proteasome pathway using single amino acid-based PROTACs; the degradation level can be adjusted by substituting different amino acids at the N-end rule recognition site, and a single PEG linker achieves the best proteolytic effect. This results in effective growth inhibition of BCR-ABL-expressing K562 cells in vitro and in a xenograft model in vivo. PROTAC-mediated protein degradation, in vitro cell proliferation assay, K562 xenograft mouse model, Western blot The Journal of biological chemistry Medium 37392851

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Translation of the Philadelphia chromosome into therapy for CML. Blood 516 19064740
2004 The biology of CML blast crisis. Blood 423 14982876
2006 ITAM-mediated tonic signalling through pre-BCR and BCR complexes. Nature reviews. Immunology 236 16557260
2013 New insights into pre-BCR and BCR signalling with relevance to B cell malignancies. Nature reviews. Immunology 235 23883968
2011 Molecular pathways: BCR-ABL. Clinical cancer research : an official journal of the American Association for Cancer Research 200 22156549
2014 Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors. Blood 198 25525119
1985 C-abl and bcr are rearranged in a Ph1-negative CML patient. The EMBO journal 182 3859408
2012 BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML: frequency and clonal relationships. Blood 179 23223358
2015 Natural course and biology of CML. Annals of hematology 172 25814077
2002 A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9. Proceedings of the National Academy of Sciences of the United States of America 161 12032333
2001 STI571: targeting BCR-ABL as therapy for CML. The oncologist 159 11423669
1987 The CML-specific P210 bcr/abl protein, unlike v-abl, does not transform NIH/3T3 fibroblasts. Science (New York, N.Y.) 150 2440107
2017 Monitoring of childhood ALL using BCR-ABL1 genomic breakpoints identifies a subgroup with CML-like biology. Blood 113 28331056
2002 Inhibition of Bcr-Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of CML cells. Oncogene 108 12483533
2011 Bcr-Abl ubiquitination and Usp9x inhibition block kinase signaling and promote CML cell apoptosis. Blood 106 21248063
2011 Kill one bird with two stones: potential efficacy of BCR-ABL and autophagy inhibition in CML. Blood 105 21693757
2009 PTEN is a tumor suppressor in CML stem cells and BCR-ABL-induced leukemias in mice. Blood 103 19965668
1996 Immunologic characterization of purified recombinant timothy grass pollen (Phleum pratense) allergens (Phl p 1, Phl p2, Phl p 5). The Journal of allergy and clinical immunology 98 8613635
2009 Epidemiology of chronic myeloid leukaemia (CML). Best practice & research. Clinical haematology 97 19959081
2005 Novel targeted therapies to overcome imatinib mesylate resistance in chronic myeloid leukemia (CML). Critical reviews in oncology/hematology 94 16213151
2005 Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML). Blood 90 16278304
2010 Regulation of BCR signaling. Molecular immunology 87 21195477
1988 bcr genes and transcripts. Oncogene 86 3285291
1987 Evidence that the phl gene encodes a 160,000-dalton phosphoprotein with associated kinase activity. Molecular and cellular biology 85 3299055
2014 Physiologic hypoxia promotes maintenance of CML stem cells despite effective BCR-ABL1 inhibition. Blood 81 24705490
2013 A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells. The Journal of clinical investigation 81 24216514
2007 The Biology of CML blast crisis. Hematology. American Society of Hematology. Education Program 70 18024655
2017 BASIC: BCR assembly from single cells. Bioinformatics (Oxford, England) 69 28172415
2017 The IgM receptor FcμR limits tonic BCR signaling by regulating expression of the IgM BCR. Nature immunology 66 28135254
2008 Imatinib resistance in CML. Cancer letters 66 18653275
2006 BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry. Leukemia 65 16572205
1987 Expression of bcr and bcr-abl fusion transcripts in normal and leukemic cells. Molecular and cellular biology 65 3670297
1997 Integrin-mediated regulation of hematopoiesis: do BCR/ABL-induced defects in integrin function underlie the abnormal circulation and proliferation of CML progenitors? Acta haematologica 63 8980609
1997 Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells. The Journal of biological chemistry 63 9195915
2011 How I treat childhood CML. Blood 61 22210880
2008 AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells. The Journal of experimental medicine 60 18936234
2016 Management of CML-blast crisis. Best practice & research. Clinical haematology 58 27839570
2022 Minimal residual disease in BCR::ABL1-positive acute lymphoblastic leukemia: different significance in typical ALL and in CML-like disease. Leukemia 53 35933523
1990 BCR-ABL and BCR proteins: biochemical characterization and localization. Leukemia 50 2232885
2009 CML in pregnancy and childhood. Best practice & research. Clinical haematology 49 19959094
2015 The interferon-alpha revival in CML. Annals of hematology 48 25814086
2010 BCR-ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients. Oncogene 48 20838376
2012 Mutated BCR-ABL generates immunogenic T-cell epitopes in CML patients. Clinical cancer research : an official journal of the American Association for Cancer Research 44 22912393
2010 BCR-ABL kinase is dead; long live the CML stem cell. The Journal of clinical investigation 44 21157035
2003 STI571 as a targeted therapy for CML. Cancer investigation 44 12901289
2021 Asciminib and ponatinib exert synergistic anti-neoplastic effects on CML cells expressing BCR-ABL1 T315I-compound mutations. American journal of cancer research 39 34659899
2014 Dual inhibition of Bcr-Abl and Hsp90 by C086 potently inhibits the proliferation of imatinib-resistant CML cells. Clinical cancer research : an official journal of the American Association for Cancer Research 39 25501124
2015 BCR/ABL1 and BCR are under the transcriptional control of the MYC oncogene. Molecular cancer 37 26179066
2015 Is there a best TKI for chronic phase CML? Blood 36 26585806
2014 ApoptomiRs expression modulated by BCR-ABL is linked to CML progression and imatinib resistance. Blood cells, molecules & diseases 36 24629639
2021 Small-molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in CML cells overcomes BCR-ABL-independent TKI resistance. Leukemia 34 34007045
1998 Bcr-Abl kinase promotes cell cycle entry of primary myeloid CML cells in the absence of growth factors. British journal of haematology 34 9488616
2010 BCR and BCR-ABL regulation during myeloid differentiation in healthy donors and in chronic phase/blast crisis CML patients. Leukemia 33 20520635
2010 Syk mediates BCR- and CD40-signaling integration during B cell activation. Immunobiology 33 21074890
1997 Pathophysiology of CML: do defects in integrin function contribute to the premature circulation and massive expansion of the BCR/ABL positive clone? The Journal of laboratory and clinical medicine 33 9178724
2018 The argument for using imatinib in CML. Hematology. American Society of Hematology. Education Program 32 30504305
2023 Single amino acid-based PROTACs trigger degradation of the oncogenic kinase BCR-ABL in chronic myeloid leukemia (CML). The Journal of biological chemistry 31 37392851
2017 Expression of CD25 on leukemic stem cells in BCR-ABL1+ CML: Potential diagnostic value and functional implications. Experimental hematology 31 28457753
2014 ATRA-induced cellular differentiation and CD38 expression inhibits acquisition of BCR-ABL mutations for CML acquired resistance. PLoS genetics 31 24967705
2007 Medical management of CML. Hematology. American Society of Hematology. Education Program 31 18024653
1989 No correlation between locations of bcr breakpoints and clinical states in Ph1-positive CML patients. Leukemia 31 2733454
1987 The BCR/ABL hybrid gene. Bailliere's clinical haematology 31 3332859
2020 The New ELN Recommendations for Treating CML. Journal of clinical medicine 29 33207600
1998 Mapping of T-cell epitopes of Phl p 5: evidence for crossreacting and non-crossreacting T-cell epitopes within Phl p 5 isoallergens. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 29 10024226
1999 Cell biology of CML cells. Leukemia 28 10232368
2019 MicroRNA signature refine response prediction in CML. Scientific reports 27 31273251
2018 We do still transplant CML, don't we? Hematology. American Society of Hematology. Education Program 27 30504307
2006 BCR ubiquitination controls BCR-mediated antigen processing and presentation. Blood 27 16931624
2017 First-line therapy for chronic phase CML: selecting the optimal BCR-ABL1-targeted TKI. Leukemia & lymphoma 26 28972424
2014 Targeting the JAK2-STAT5 pathway in CML. Blood 26 25170113
2012 Detection of Phl p 1, Phl p 5, Phl p 7 and Phl p 12 specific IgE antibodies in the sera of children and adult patients allergic to Phleum pollen. Allergology international : official journal of the Japanese Society of Allergology 26 22526205
2011 BCR-ABL- and Ras-independent activation of Raf as a novel mechanism of Imatinib resistance in CML. International journal of oncology 26 21637917
2008 FISH mapping of Philadelphia negative BCR/ABL1 positive CML. Molecular cytogenetics 26 18638369
1987 Chromosome abnormalities in CML. Bailliere's clinical haematology 26 3332858
2014 IRF5 is a target of BCR-ABL kinase activity and reduces CML cell proliferation. Carcinogenesis 25 24445143
2011 Down-regulation of Thanatos-associated protein 11 by BCR-ABL promotes CML cell proliferation through c-Myc expression. International journal of cancer 24 21400515
2010 Dysregulated calcium homeostasis and oxidative stress in chronic myeloid leukemia (CML) cells. Journal of cellular physiology 24 20432440
2006 Not all imatinib resistance in CML are BCR-ABL kinase domain mutations. Annals of hematology 24 17006667
2005 B cell receptor (BCR) cross-talk: CD40 engagement enhances BCR-induced ERK activation. Journal of immunology (Baltimore, Md. : 1950) 24 15749869
2020 Digital PCR for BCR-ABL1 Quantification in CML: Current Applications in Clinical Practice. HemaSphere 23 33283168
2009 Initial treatment for patients with CML. Hematology. American Society of Hematology. Education Program 23 20008231
2021 TCR+/BCR+ dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes. Cell 22 33545036
2017 Novel approaches to therapy in CML. Hematology. American Society of Hematology. Education Program 22 29222245
2015 Evolution of BCR/ABL gene mutation in CML is time dependent and dependent on the pressure exerted by tyrosine kinase inhibitor. PloS one 21 25629972
2002 Bcr: a negative regulator of the Bcr-Abl oncoprotein in leukemia. Oncogene 21 12476302
2020 Bcr-Abl Tyrosine Kinase Inhibitors in the Treatment of Pediatric CML. International journal of molecular sciences 20 32586039
2018 Molecular monitoring in CML: how deep? How often? How should it influence therapy? Hematology. American Society of Hematology. Education Program 20 30504306
2024 Navigating the Management of Chronic Phase CML in the Era of Generic BCR::ABL1 Tyrosine Kinase Inhibitors. Journal of the National Comprehensive Cancer Network : JNCCN 19 38394773
2022 The progress of small-molecules and degraders against BCR-ABL for the treatment of CML. European journal of medicinal chemistry 19 35551036
2023 Resistance mutations in CML and how we approach them. Hematology. American Society of Hematology. Education Program 18 38066920
2016 FZD7 regulates BMSCs-mediated protection of CML cells. Oncotarget 18 26716419
2009 Treatment strategies for CML. Best practice & research. Clinical haematology 18 19959082
2006 The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells. Blood 18 16849647
2003 Current CML therapy: progress and dilemma. Leukemia 18 12764362
2023 Higher-order interactions of Bcr-Abl can broaden chronic myeloid leukemia (CML) drug repertoire. Protein science : a publication of the Protein Society 17 36369657
2015 Molecular characterization and follow-up of five CML patients with new BCR-ABL1 fusion transcripts. Genes, chromosomes & cancer 17 26252834
2011 In search of CML stem cells' deadly weakness. Current hematologic malignancy reports 17 21373837
2011 Hurdles toward a cure for CML: the CML stem cell. Hematology/oncology clinics of North America 17 22054728
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