Affinage

CRLF2

Cytokine receptor-like factor 2 · UniProt Q9HC73

Length
371 aa
Mass
42.0 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRLF2 (TSLPR) encodes a type I cytokine receptor subunit bearing two fibronectin type III-like domains, a WSXWS-like motif, and intracellular box1/box2 motifs that heterodimerizes with the IL-7 receptor alpha chain to form the functional receptor for TSLP (PMID:11474172, PMID:11237741, PMID:11891057). Originally characterized as a receptor expressed by dendritic cells and activated monocytes whose surface levels rise upon LPS stimulation (PMID:11237741), CRLF2 is best defined mechanistically as a driver of B-cell progenitor leukemogenesis: rearrangement (P2RY8-CRLF2) or overexpression activates the JAK-STAT pathway and confers cytokine-independent proliferation, cooperating with activating JAK2 mutations and acting as the obligate scaffold for mutant JAK2 signaling in B-ALL (PMID:19838194, PMID:19641190, PMID:20018760). An activating F232C mutation drives constitutive receptor dimerization and growth through a mechanism distinct from TSLP- or mutant-JAK2-driven signaling, with the three modes differing in their dependence on specific intracellular tyrosines (F232C requires Y368) while all require the box1 domain and intracellular tryptophan W286 (PMID:20018760, PMID:19965641, PMID:22915648). Downstream, CRLF2 engages a coordinated network of JAK/STAT5 and PI3K/AKT/mTOR signaling, interconnected such that JAK inhibition also abrogates PI3K/mTOR phosphorylation (PMID:22685175, PMID:26611474), together with co-activated CREB, MAPK/ERK, RAS (via CRKL), and IGF1R/FGFR1 signaling (PMID:29796158, PMID:32801162, PMID:34587248). CRLF2 transcription is directly repressed by Ikaros (IKZF1), which binds the CRLF2 promoter and deposits H3K9me3 (PMID:27391346). TSLP also signals through TSLPR-dependent PI3K/Akt to promote platelet activation and thrombus formation (PMID:25591759).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 Medium

    Established the molecular identity of CRLF2 as a type I cytokine receptor and mapped it to the pseudoautosomal region, defining the structural framework for its receptor function.

    Evidence cDNA cloning, sequence analysis, and FISH mapping; expression profiling in dendritic cells and monocytes with LPS induction

    PMID:11237741 PMID:11474172

    Open questions at the time
    • Ligand and dimerization partner not yet identified
    • Signaling output uncharacterized
  2. 2002 Medium

    Identified CRLF2/TSLPR as the heterodimeric partner of IL-7Ralpha that constitutes the functional TSLP receptor, defining its physiological signaling complex.

    Evidence Cloning, cross-species sequence alignment, and receptor reconstitution assays

    PMID:11891057

    Open questions at the time
    • Intracellular signaling residues not mapped
    • Downstream pathways not defined
  3. 2009 High

    Demonstrated that CRLF2 rearrangement/overexpression drives leukemic transformation by activating JAK-STAT and conferring cytokine-independent growth, cooperating with JAK2 mutations and serving as the scaffold for mutant JAK2.

    Evidence Ba/F3 transformation assays, retroviral co-expression of P2RY8-CRLF2 and mutant JAK2, primary B-progenitor transduction, and IL-3-substitution screen with patient validation

    PMID:19641190 PMID:19838194 PMID:20018760

    Open questions at the time
    • Mechanistic basis distinguishing ligand- vs mutation-driven signaling not resolved
    • Downstream effectors beyond STAT undefined
  4. 2009 High

    Identified the F232C gain-of-function mutation as an activating lesion driving constitutive receptor dimerization, revealing a JAK2-mutation-independent oncogenic mechanism.

    Evidence Site-directed mutagenesis with Ba/F3 growth and phospho-JAK2 readouts, replicated across patient samples

    PMID:19965641 PMID:20018760

    Open questions at the time
    • Kinase mediating F232C signaling not pinpointed at this stage
    • Structural basis of dimerization not solved
  5. 2010 Medium

    Mapped the intracellular tyrosine requirements for TSLP signaling, showing redundancy between IL-7Ralpha and CRLF2 cytoplasmic tyrosines in proliferative signaling.

    Evidence Systematic mutagenesis of cytoplasmic tyrosines with Ba/F3 TSLP-dependent proliferation assays

    PMID:20144186

    Open questions at the time
    • Identity of tyrosine-binding effectors not determined
    • Single-lab finding
  6. 2012 High

    Dissected three distinct CRLF2 oncogenic signaling modes (TSLP, F232C, mutant JAK2), showing shared dependence on box1/W286 but divergent tyrosine requirements, and demonstrated interconnection of JAK/STAT and PI3K/mTOR networks.

    Evidence Domain/residue mutagenesis with proliferation readout and quantitative phosphotyrosine analysis; phospho-flow of primary ALL with JAK inhibition

    PMID:22685175 PMID:22915648

    Open questions at the time
    • Precise adaptor coupling box1 to JAK not defined
    • Crosstalk node linking JAK to PI3K not identified
  7. 2015 Medium

    Established species-specific TSLP-receptor interaction and extended TSLPR signaling beyond leukemia to platelet activation via PI3K/Akt.

    Evidence TSLP stimulation of PDX cells comparing human vs mouse ligand; TSLPR knockout mouse platelet and thrombosis assays

    PMID:25591759 PMID:26611474

    Open questions at the time
    • Structural basis of species specificity unresolved
    • Platelet TSLPR complex composition not defined
  8. 2016 Medium

    Identified transcriptional control of CRLF2 by Ikaros, defining an epigenetic repression mechanism via H3K9me3 deposition at the CRLF2 promoter.

    Evidence ChIP, CK2 inhibitor treatment, siRNA knockdown, and H3K9me3 ChIP in ALL cells

    PMID:27391346

    Open questions at the time
    • Cofactors of Ikaros-mediated repression not identified
    • Single-lab finding
  9. 2021 High

    Defined cooperating oncogenic and therapeutic vulnerabilities, including HMGN1 cooperation in transformation and rational JAK-degrading PROTAC design enabled by JAK2 crystal structures.

    Evidence Ba/F3 transformation with HMGN1 plus inducible CRISPR KO xenograft; JAK2-inhibitor crystal structures with PROTAC synthesis and xenograft testing

    PMID:34110416 PMID:34857887

    Open questions at the time
    • Mechanism of HMGN1 cooperation not detailed
    • Resistance to PROTAC degradation not assessed
  10. 2022 Medium

    Genome-wide and mechanistic studies refined the essential signaling components downstream of CRLF2, showing STAT5/STAT3 dispensability but JAK/IL7RA/RAS-CRKL dependence, and characterized E2F-driven differentiation block.

    Evidence Genome-wide CRISPR dropout screen with CRKL depletion; Dp16 Down syndrome B-progenitor colony assays and gene expression profiling

    PMID:34587248 PMID:35306048

    Open questions at the time
    • Role of RAS/CRKL relative to JAK signaling not fully delineated
    • Single-lab findings
  11. 2022 Medium

    Mapped the broader CRLF2 phosphotyrosine network and identified mechanisms of and routes to overcome therapeutic resistance.

    Evidence SILAC phosphotyrosine profiling identifying IGF1R/FGFR1 and Rap1; CyTOF mapping of JAK/STAT-PI3K-CREB network with SRC/ABL inhibition; high-dose TSLP receptor downregulation; BCL6/TP53 resistance axis with FX1

    PMID:29796158 PMID:32801162 PMID:36005560 PMID:36613920

    Open questions at the time
    • Hierarchy among the many activated kinases unclear
    • Translational durability of combination strategies unestablished

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of CRLF2/IL-7Ralpha heterodimer assembly and how distinct activating lesions reshape the receptor to couple to specific kinases and downstream effectors remains incompletely resolved.
  • No high-resolution structure of the assembled CRLF2 receptor complex in the corpus
  • Direct adaptor coupling box1/W286 to JAK activation not defined
  • Mechanism integrating JAK/STAT, PI3K, RAS, and IGF1R/FGFR1 outputs unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2 R-HSA-109582 Hemostasis 1
Partners
CRKLHMGN1IKZF1IL7RJAK1JAK2STAT5
Complex memberships
TSLP receptor (CRLF2/IL-7Ralpha heterodimer)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 CRLF2 rearrangement (P2RY8-CRLF2 fusion) co-operates with activating JAK2 mutations to cause constitutive JAK-STAT activation and cytokine-independent growth; expression of P2RY8-CRLF2 together with mutated Jak2 in Ba/F3 cells overexpressing IL-7Rα resulted in constitutive Jak-Stat activation and cytokine-independent proliferation. Ba/F3 cell transformation assay; retroviral co-expression of P2RY8-CRLF2 and mutant Jak2 Nature genetics High 19838194
2009 CRLF2 overexpression activates the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation, indicating a causal role in lymphoid transformation. Retroviral transduction of primary B-cell progenitors with CRLF2; JAK-STAT phosphorylation assays; proliferation assays Blood High 19641190
2009 CRLF2 encodes a type I cytokine receptor subunit that, when overexpressed, can substitute for IL-3 signaling in a functional screen; CRLF2 acts as the key scaffold for mutant JAK2 signaling in B-ALL, since all 22 B-ALLs with mutant JAK2 overexpressed CRLF2. Functional mRNA screen for IL-3 signaling substitution; Ba/F3 cytokine-independent growth assay; phospho-JAK2 analysis Proceedings of the National Academy of Sciences of the United States of America High 20018760
2009 A gain-of-function CRLF2 F232C mutation promotes constitutive receptor dimerization and cytokine-independent growth in Ba/F3 cells; this differs mechanistically from WT CRLF2/mutant JAK2 signaling (which involves JAK2 phosphorylation) versus CRLF2 F232C (which does not involve JAK2 phosphorylation). Ba/F3 cytokine-independent growth assay; phospho-JAK2 Western blotting; site-directed mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 19965641 20018760
2009 CRLF2 and mutated JAK2 cooperate in conferring cytokine-independent growth to BaF3 pro-B cells; the F232C mutation in CRLF2 was identified as an activating somatic mutation. Ba/F3 transformation assay; retroviral co-expression of CRLF2 variants and mutant JAK2 Blood High 19965641
2001 CRLF2 was identified as a type I cytokine receptor with an extracellular domain containing two fibronectin type III-like domains, four conserved cysteine residues, a WSXWS box-like motif, and an intracellular domain containing box 1 and box 2-like motifs; the gene is located in the pseudoautosomal region Xp22.3/Yp11.3. cDNA cloning from T-lymphocyte library; sequence analysis; FISH mapping Cytogenetics and cell genetics Medium 11237741 11474172
2001 CRLF2 (CRL2) is a type I transmembrane cytokine receptor preferentially expressed by dendritic cells and activated monocytes; its expression is upregulated by LPS stimulation of monocytes; the intracellular domain contains a box 1 motif and a conserved tyrosine potentially binding signal-transducing molecules. cDNA library screening; RT-PCR; Northern blot; LPS stimulation; Ba/F3 transfection with FLAG-tagged CRLF2; immunoprecipitation Biochemical and biophysical research communications Medium 11237741
2002 TSLPR (CRLF2) forms a heterodimeric complex with the IL-7 receptor alpha chain to form the functional receptor for TSLP; the WSXWX motif is conserved across mouse, rat, and human TSLPR; alternative splicing produces two functional receptor variants in mice. Cloning; sequence alignment; zooblot; alternative splice variant analysis; receptor reconstitution assays Gene Medium 11891057
2010 TSLP-dependent cell proliferation requires at least one cytoplasmic tyrosine residue in either IL-7Rα or CRLF2; the single tyrosine residue in human CRLF2 alone is NOT required for TSLP-dependent proliferation; tyrosine residues in IL-7Rα and CRLF2 play redundant roles in TSLP-mediated growth signaling. Site-directed mutagenesis of IL-7Rα and CRLF2 cytoplasmic tyrosines; Ba/F3 TSLP-dependent proliferation assay BMC immunology Medium 20144186
2012 CRLF2 signaling through three distinct mechanisms (TSLP stimulation, CRLF2 F232C mutation, and CRLF2/mutant JAK2) differs at the level of intracellular tyrosines: CRLF2 F232C requires intracellular tyrosine Y368, while TSLP- or mutant JAK2-driven signaling does not; all three modes require the CRLF2 box1 domain and intracellular tryptophan W286. Domain mutation analysis; Ba/F3 proliferation assay; global quantitative phosphotyrosine analysis; Western blotting Blood High 22915648
2012 CRLF2-rearranged ALL exhibits elevated basal pJAK2, pSTAT5, and pS6; TSLP stimulation of these leukemias induces robust JAK/STAT and PI3K/mTOR pathway signaling; JAK inhibition also abrogates PI3K/mTOR pathway phosphorylation, indicating interconnection between these signaling networks. Phospho-flow cytometry of primary ALL samples; TSLP stimulation assays; JAK inhibitor treatment with pathway readout Blood High 22685175
2015 TSLP stimulates human CRLF2-overexpressing ALL via JAK/STAT5 and PI3K/AKT/mTOR pathways; mouse TSLP does NOT activate these downstream pathways in human CRLF2-rearranged ALL, demonstrating species-specific ligand–receptor interaction. TSLP stimulation of patient-derived xenograft samples; JAK/STAT5 and PI3K/AKT/mTOR phosphorylation assays; comparison of human vs. mouse TSLP Haematologica Medium 26611474
2015 TSLP stimulates platelet activation and thrombus formation via a TSLPR-dependent PI3K/Akt signaling pathway; TSLPR is expressed on murine platelets, and TSLPR-deficient platelets show defective aggregation, secretion, and in vivo thrombus formation. Western blotting; flow cytometry; TSLPR knockout mice; perfusion chambers; FeCl3 carotid artery thrombosis model; PI3K inhibitor assays Cellular physiology and biochemistry Medium 25591759
2016 Ikaros (IKZF1-encoded protein) directly binds the CRLF2 promoter and represses CRLF2 transcription; CK2 inhibitor increases Ikaros binding to the CRLF2 promoter and suppresses CRLF2 expression in an Ikaros-dependent manner; this repression is associated with increased H3K9me3 histone modifications at the CRLF2 promoter. ChIP assay; CK2 inhibitor treatment; siRNA knockdown; H3K9me3 ChIP in ALL cell lines and primary cells Oncotarget Medium 27391346
2021 HMGN1 overexpression in combination with P2RY8-CRLF2 in Ba/F3 cells results in cytokine-independent transformation and upregulation of cell signaling pathways associated with leukemic development; HMGN1 knockout mitigates CRLF2-rearranged leukemia burden in vivo. Ba/F3 transformation assay; inducible CRISPR/Cas9 knockout xenograft model; in vivo engraftment studies Oncogene Medium 34857887
2022 CRLF2 overexpression in Dp16 (Down syndrome model) B-progenitor cells results in enhanced immature B-lymphoid colony development and reduced B-cell differentiation, associated with a gene expression signature of E2F signaling; PI3K/mTOR and pan-CDK inhibitors show cytotoxicity in CRLF2-rearranged B-ALL. Dp16 mouse model; colony assays; gene expression profiling; inhibitor cytotoxicity assays in cell lines and patient samples Experimental hematology Medium 35306048
2019 CRLF2-rearranged Ph-like ALL leukemia cells demonstrate relative glucocorticoid resistance; inhibition of MEK (trametinib) or Akt (MK2206), but NOT JAK inhibition (ruxolitinib), is sufficient to augment glucocorticoid sensitivity, indicating that MAPK/Akt rather than JAK-STAT signaling mediates GC resistance downstream of CRLF2. Patient-derived xenograft GC sensitivity assays; targeted inhibitor studies with MEK, Akt, and JAK inhibitors PloS one Medium 31318944
2021 JAK-directed PROTACs (proteolysis-targeting chimeras) degrade JAKs and potently kill CRLF2-rearranged ALL cell lines; solving crystal structures of type I JAK inhibitors ruxolitinib and baricitinib bound to the JAK2 tyrosine kinase domain enabled rational PROTAC design; dual JAK/GSPT1-degrading PROTACs were most potent, with JAK2-degrading, GSPT1-sparing PROTACs also efficacious in kinase-driven xenografts. Crystal structure determination of JAK2-inhibitor complexes; PROTAC synthesis and testing; cell viability assays; xenograft models Blood High 34110416
2022 Genome-wide CRISPR-Cas9 dropout screens showed that STAT5A, STAT5B, and STAT3 are largely dispensable for IgH-CRLF2-rearranged ALL cell survival, while CRLF2, IL7RA, JAK1/2, and RAS signaling regulators (particularly CRKL) are critical; CRKL depletion enhances ruxolitinib sensitivity in RAS wild-type cells. Genome-wide CRISPR-Cas9 dropout screen; sgRNA fitness analysis; CRKL depletion experiments Blood Medium 34587248
2022 High-dose TSLP induced apoptosis and loss of CRLF2 receptor expression in CRLF2 B-ALL cell lines in vitro, and prevented engraftment/prolonged survival in patient-derived xenograft mice; mechanistically, high TSLP doses caused receptor downregulation and loss of downstream CRLF2 signaling. In vitro cell line apoptosis assay; patient-derived xenograft in vivo model; receptor surface expression by flow cytometry; signaling pathway Western blotting International journal of molecular sciences Medium 36613920
2023 CRLF2-rearranged leukemia treated with ruxolitinib upregulates BCL6, which suppresses TP53 and pro-apoptotic molecules (FAS, TNFRSF10B, BID, BAX, BAK, PUMA, NOXA), conferring resistance; BCL6 inhibition combined with ruxolitinib restores TP53 expression, enhances apoptosis, and prolongs survival in xenografted mice. Gene expression analysis post-ruxolitinib treatment; BCL6 inhibitor (FX1) experiments; Western blotting for TP53 and apoptotic markers; xenograft survival assay Haematologica Medium 36005560
2018 In CRLF2-overexpressing B-ALL, a coordinated signaling network downstream of CRLF2 involves co-activation of JAK/STAT, PI3K, and CREB pathways; this network can be more effectively disrupted by SRC/ABL inhibition than by single-agent JAK or PI3K inhibition. Single-cell mass cytometry (CyTOF) on 15 primary patient samples; SRC/ABL inhibitor functional assays including in MRD cells Oncotarget Medium 29796158
2020 TSLP stimulation of CRLF2-rearranged Ph-like ALL cells activates JAK1, JAK2, STAT5, ERK1/2, IGF1R, and FGFR1 phosphotyrosine signaling, as well as the Rap1 signaling pathway; phosphotyrosine profiling identified IGF1R and FGFR1 as novel TSLP-activated kinases in this context. Phosphotyrosine (P-Tyr) profiling with SILAC; TSLP stimulation of CRLF2-rearranged cell lines; tyrosine kinase inhibitor synergy assays Molecular cancer research Medium 32801162

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nature genetics 459 19838194
2010 Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Blood 444 20139093
2009 Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood 375 19641190
2009 Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proceedings of the National Academy of Sciences of the United States of America 270 20018760
2009 Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood 265 19965641
2012 Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children's Oncology Group study. Blood 195 22368272
2012 Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia. Blood 191 22685175
2018 C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases. Molecular cell 152 29775578
2010 Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial. Blood 112 21106984
2015 Eradication of B-ALL using chimeric antigen receptor-expressing T cells targeting the TSLPR oncoprotein. Blood 106 26041741
2012 IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and adults with acute lymphoblastic leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 106 22851563
2017 CRL2Lrr1 promotes unloading of the vertebrate replisome from chromatin during replication termination. Genes & development 97 28235849
2012 Outcome in children with Down's syndrome and acute lymphoblastic leukemia: role of IKZF1 deletions and CRLF2 aberrations. Leukemia 87 22441210
2018 Recognition of the Diglycine C-End Degron by CRL2KLHDC2 Ubiquitin Ligase. Molecular cell 86 30526872
2011 Function and mechanisms of TSLP/TSLPR complex in asthma and COPD. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 72 22168549
2011 A soluble thymic stromal lymphopoietin (TSLP) antagonist, TSLPR-immunoglobulin, reduces the severity of allergic disease by regulating pulmonary dendritic cells. Clinical and experimental immunology 67 21352203
2021 Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia. Blood 65 34110416
2015 SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding. Science (New York, N.Y.) 62 26138980
2012 IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation. Clinical and molecular allergy : CMA 57 22838633
2012 Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2-harboring clones as main relapse-driving force in childhood ALL. Blood 54 23091296
2010 CRLF2 and JAK2 in B-progenitor acute lymphoblastic leukemia: a novel association in oncogenesis. Cancer research 54 20807819
2001 Molecular cloning of a human novel type I cytokine receptor related to delta1/TSLPR. Cytogenetics and cell genetics 54 11474172
2010 CRL2(LRR-1) targets a CDK inhibitor for cell cycle control in C. elegans and actin-based motility regulation in human cells. Developmental cell 53 21074724
2017 Characterisation of the genomic landscape of CRLF2-rearranged acute lymphoblastic leukemia. Genes, chromosomes & cancer 52 28033648
2017 CRLF2-Positive B-Cell Acute Lymphoblastic Leukemia in Adult Patients: A Single-Institution Experience. American journal of clinical pathology 47 28340183
2016 Genomic and transcriptional landscape of P2RY8-CRLF2-positive childhood acute lymphoblastic leukemia. Leukemia 46 27899802
2018 Inhibition of mTORC1/C2 signaling improves anti-leukemia efficacy of JAK/STAT blockade in CRLF2 rearranged and/or JAK driven Philadelphia chromosome-like acute B-cell lymphoblastic leukemia. Oncotarget 44 29487712
2015 CRLF2 overexpression identifies an unfavourable subgroup of adult B-cell precursor acute lymphoblastic leukemia lacking recurrent genetic abnormalities. Leukemia research 43 26754556
2012 Differences in signaling through the B-cell leukemia oncoprotein CRLF2 in response to TSLP and through mutant JAK2. Blood 40 22915648
2021 Molecular basis for recognition of Gly/N-degrons by CRL2ZYG11B and CRL2ZER1. Molecular cell 36 34214466
2020 NRBP1-Containing CRL2/CRL4A Regulates Amyloid β Production by Targeting BRI2 and BRI3 for Degradation. Cell reports 36 32160551
2016 High CRLF2 expression associates with IKZF1 dysfunction in adult acute lymphoblastic leukemia without CRLF2 rearrangement. Oncotarget 36 27391346
2017 The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL. Leukemia 35 28331226
2013 CRL2(LRR-1) E3-ligase regulates proliferation and progression through meiosis in the Caenorhabditis elegans germline. PLoS genetics 35 23555289
2012 Treatment outcome of CRLF2-rearranged childhood acute lymphoblastic leukaemia: a comparative analysis of the AIEOP-BFM and UK NCRI-CCLG study groups. British journal of haematology 35 22816614
2021 Molecular basis for ubiquitin ligase CRL2FEM1C-mediated recognition of C-degron. Nature chemical biology 33 33398170
2021 CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptosis through promoting p14ARF degradation. Cell death and differentiation 33 34743205
2011 Understanding the biology of CRLF2-overexpressing acute lymphoblastic leukemia. Critical reviews in oncogenesis 33 22150304
2017 Lipopolysaccharide-Elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14+ CD1c+ Monocytes. Journal of immunology (Baltimore, Md. : 1950) 29 28341671
2021 Combination efficacy of ruxolitinib with standard-of-care drugs in CRLF2-rearranged Ph-like acute lymphoblastic leukemia. Leukemia 27 33895784
2014 An overall characterization of pediatric acute lymphoblastic leukemia with CRLF2 overexpression. Genes, chromosomes & cancer 27 24935070
2016 Atlas on substrate recognition subunits of CRL2 E3 ligases. Oncotarget 26 27107416
2001 Identification of a novel type I cytokine receptor CRL2 preferentially expressed by human dendritic cells and activated monocytes. Biochemical and biophysical research communications 26 11237741
2022 CRL2ZER1/ZYG11B recognizes small N-terminal residues for degradation. Nature communications 25 36496439
2021 Tumor-associated antigen Prame targets tumor suppressor p14/ARF for degradation as the  receptor protein of CRL2Prame complex. Cell death and differentiation 25 33504946
2015 A novel xenograft model to study the role of TSLP-induced CRLF2 signals in normal and malignant human B lymphopoiesis. Haematologica 25 26611474
2019 CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition. PloS one 24 31318944
2017 Differential expression of MUC4, GPR110 and IL2RA defines two groups of CRLF2-rearranged acute lymphoblastic leukemia patients with distinct secondary lesions. Cancer letters 22 28866095
2019 Short ragweed pollen promotes M2 macrophage polarization via TSLP/TSLPR/OX40L signaling in allergic inflammation. Mucosal immunology 21 31350466
2021 UBXN7 cofactor of CRL3KEAP1 and CRL2VHL ubiquitin ligase complexes mediates reciprocal regulation of NRF2 and HIF-1α proteins. Biochimica et biophysica acta. Molecular cell research 20 33444648
2021 HMGN1 plays a significant role in CRLF2 driven Down Syndrome leukemia and provides a potential therapeutic target in this high-risk cohort. Oncogene 20 34857887
2018 Single-cell analysis identifies CRLF2 rearrangements as both early and late events in Down syndrome and non-Down syndrome acute lymphoblastic leukaemia. Leukemia 20 30487598
2024 Mechanism of Ψ-Pro/C-degron recognition by the CRL2FEM1B ubiquitin ligase. Nature communications 19 38670995
2015 Inflammatory cytokine TSLP stimulates platelet secretion and potentiates platelet aggregation via a TSLPR-dependent PI3K/Akt signaling pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 19 25591759
2023 Mechanism and evolutionary origins of alanine-tail C-degron recognition by E3 ligases Pirh2 and CRL2-KLHDC10. Cell reports 18 37676773
2023 CRL2APPBP2-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence. Science China. Life sciences 18 38170390
2016 A potential link between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in human corneal epithelial cells for Aspergillus fumigatus tolerance. Molecular immunology 18 26874828
2022 Genome-wide CRISPR-Cas9 screen identifies rationally designed combination therapies for CRLF2-rearranged Ph-like ALL. Blood 17 34587248
2014 Disruption of the TSLP-TSLPR-LAP signaling between epithelial and dendritic cells through hyperlipidemia contributes to regulatory T-Cell defects in atherosclerotic mice. Atherosclerosis 17 25544178
2023 Molecular basis for C-degron recognition by CRL2APPBP2 ubiquitin ligase. Proceedings of the National Academy of Sciences of the United States of America 14 37844242
2021 Hematological characteristics, cytogenetic features, and post-induction measurable residual disease in thymic stromal lymphopoietin receptor (TSLPR) overexpressed B-cell acute lymphoblastic leukemia in an Indian cohort. Annals of hematology 14 34159401
2014 TSLPR deficiency attenuates atherosclerotic lesion development associated with the inhibition of TH17 cells and the promotion of regulator T cells in ApoE-deficient mice. Journal of molecular and cellular cardiology 14 25117469
2023 Clinical, biological, and outcome features of P2RY8-CRLF2 and CRLF2 over-expression in pediatric B-cell precursor acute lymphoblastic leukemia according to the CCLG-ALL 2008 and 2018 protocol. European journal of haematology 12 36814093
2022 CRL2KLHDC3 mediates p14ARF N-terminal ubiquitylation degradation to promote non-small cell lung carcinoma progression. Oncogene 12 35468939
2022 Nonylphenol exacerbates ovalbumin-induced allergic rhinitis via the TSLP-TSLPR/IL-7R pathway and JAK1/2-STAT3 signaling in a mouse model. Ecotoxicology and environmental safety 12 36029577
2021 Quantitative analyses for effects of neddylation on CRL2VHL substrate ubiquitination and degradation. Protein science : a publication of the Protein Society 12 34459035
2025 Identification of a non-inhibitory aptameric ligand to CRL2ZYG11B E3 ligase for targeted protein degradation. Nature communications 11 40082426
2023 BCL6 inhibition ameliorates resistance to ruxolitinib in CRLF2-rearranged acute lymphoblastic leukemia. Haematologica 11 36005560
2020 Combinatorial IL-17RB, ST2, and TSLPR Signaling in Dendritic Cells of Patients With Allergic Rhinitis. Frontiers in cell and developmental biology 11 32309281
2018 SRC/ABL inhibition disrupts CRLF2-driven signaling to induce cell death in B-cell acute lymphoblastic leukemia. Oncotarget 11 29796158
2014 Gene alterations involving the CRLF2-JAK pathway and recurrent gene deletions in Down syndrome-associated acute lymphoblastic leukemia in Japan. Genes, chromosomes & cancer 11 25044358
2010 Site-directed mutagenesis reveals a unique requirement for tyrosine residues in IL-7Ralpha and TSLPR cytoplasmic domains in TSLP-dependent cell proliferation. BMC immunology 11 20144186
2022 High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia. Cytokine 10 35537330
2017 Whole-Genome Sequencing of a Family with Hereditary Pulmonary Alveolar Proteinosis Identifies a Rare Structural Variant Involving CSF2RA/CRLF2/IL3RA Gene Disruption. Scientific reports 10 28233860
2017 Philadelphia Chromosome-like Mixed-Phenotype Acute Leukemia Demonstrating P2RY8-CRLF2 Fusion and JAK1 Mutation. American journal of clinical pathology 10 29140408
2017 Virtual screening for inhibitors of the human TSLP:TSLPR interaction. Scientific reports 10 29222519
2017 TSLP/TSLPR promote angiogenesis following ischemic stroke via activation of the PI3K/AKT pathway. Molecular medicine reports 10 29257253
2023 Gain of chromosome 21 increases the propensity for P2RY8::CRLF2 acute lymphoblastic leukemia via increased HMGN1 expression. Frontiers in oncology 9 37483494
2024 Co-targeting of the thymic stromal lymphopoietin receptor to decrease immunotherapeutic resistance in CRLF2-rearranged Ph-like and Down syndrome acute lymphoblastic leukemia. Leukemia 8 39681640
2023 Preclinical development of 1B7/CD3, a novel anti-TSLPR bispecific antibody that targets CRLF2-rearranged Ph-like B-ALL. Leukemia 8 37634013
2019 GATA3 germline variant is associated with CRLF2 expression and predicts outcome in pediatric B-cell precursor acute lymphoblastic leukemia. Genes, chromosomes & cancer 8 30859636
2024 Comprehensive detection of CRLF2 alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach. Frontiers in molecular biosciences 7 38370004
2023 TSLP/TSLPR promotes renal fibrosis by activating STAT3 in renal fibroblasts. International immunopharmacology 7 37364323
2022 CRLF2 overexpression defines an immature-like subgroup which is rescued through restoration of the PRC2 function in T-cell precursor acute lymphoblastic leukemia. Genes, chromosomes & cancer 7 35253299
2013 Anti-CRLF2 Antibody-Armored Biodegradable Nanoparticles for Childhood B-ALL. Particle & particle systems characterization : measurement and description of particle properties and behavior in powders and other disperse systems 7 23976822
2002 Cloning of rat thymic stromal lymphopoietin receptor (TSLPR) and characterization of genomic structure of murine Tslpr gene. Gene 7 11891057
2024 CRLF2-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy. Journal for immunotherapy of cancer 6 39461880
2022 CRLF2 overexpression results in reduced B-cell differentiation and upregulated E2F signaling in the Dp16 mouse model of Down syndrome. Experimental hematology 6 35306048
2021 CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways. The journal of pathology. Clinical research 6 33890726
2018 Precision medicine approaches may be the future for CRLF2 rearranged Down Syndrome Acute Lymphoblastic Leukaemia patients. Cancer letters 6 29879498
2010 Identifying the polymorphisms in the thymic stromal lymphopoietin receptor (TSLPR) and their association with asthma. BMB reports 6 20663412
2024 CRL2KLHDC3 and CRL1Fbxw7 cooperatively mediate c-Myc degradation. Oncogene 5 38698266
2022 TSLP as a Potential Therapy in the Treatment of CRLF2 B Cell Acute Lymphoblastic Leukemia. International journal of molecular sciences 5 36613920
2021 A recombinant antibody fragment directed to the thymic stromal lymphopoietin receptor (CRLF2) efficiently targets pediatric Philadelphia chromosome-like acute lymphoblastic leukemia. International journal of biological macromolecules 5 34481852
2025 TSLP and TSLPr Expression and Localization in the Airways of COPD and Non-COPD Patients. European journal of immunology 4 39821119
2023 An intrinsic network of polar interactions is responsible for binding of UL49.5 C-degron by the CRL2KLHDC3 ubiquitin ligase. Proteins 4 38069558
2022 Metal Allergy Mediates the Development of Oral Lichen Planus via TSLP-TSLPR Signaling. Journal of clinical medicine 4 35159975
2021 Characterization of CRLF2 Expression in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia. Clinical laboratory 4 33491417
2020 Targeting TSLP-Induced Tyrosine Kinase Signaling Pathways in CRLF2-Rearranged Ph-like ALL. Molecular cancer research : MCR 4 32801162
2019 CRLF2 expression associates with ICN1 stabilization in T-cell acute lymphoblastic leukemia. Genes, chromosomes & cancer 4 30578688

Missed literature

Know a paper Affinage missed for CRLF2? Flag it for the maintainers and the community.

No submissions yet.