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. Author manuscript; available in PMC: 2018 Jul 11.
Published in final edited form as: Semin Oncol. 2017 Jul 11;44(2):101–112. doi: 10.1053/j.seminoncol.2017.06.005

Table 7.

Role of cadherins in mediating chemoresistance in hematologic malignancies

Cell type/cadherin Consequences Reference/s
B-cell ALL/VE Cadherin (CD144)

  • VE-cadherin expressed in Ph+ leukemia cells mediates chemotherapy resistance by increasing expression of β-catenin and in turn resulting in nuclear localization and activation of β –catenin

  • β-catenin/Wnt signaling pathway is essential for Ph+ leukemia stem cell survival, and has been identified as a contributor to chemoresistance in ALL
B-cell ALL/N- Cadherin (CD325)

  • N-cadherin is involved in adhesion of E2A-PBX1 positive B-ALL cells to stromal cells.

  • N-cadherin expression is increased in the population of Bcr/Abl transformed ALL cells that survive treatment with farnesyltransferase inhibitor in co-culture with fibroblasts

  • N-cadherin expression sufficient to induce chemoresistance in the population of Bcr/Abl transformed lymphoblastic leukemia cells

  • Gene expression profiling analyses have shown N-cadherin overexpression in B-ALL cells compared to normal lymphoblasts; N-cadherin could be exploited to specifically target ALL cells
T-cell ALL/N- Cadherin (CD325)

  • Gene expression profiling analyses has shown N-cadherin overexpression in T-ALL cells compared to normal lymphoblasts; N-cadherin could be exploited to specifically target ALL cells
AML/N-cadherin (CD325)

  • In AML patients, N-cadherin expressing leukemia stem cells were resistant to chemotherapy and greatly enriched following induction therapy

  • N-cadherin expressing AML stem cells engraft faster in NOD/SCID mice
CML/N-cadherin (CD325)

  • N-cadherin mediated adhesion in CML cells co-cultured with stromal cells protects CML cells from apoptotic cell death induced by treatment with tyrosine kinase inhibitors
Multiple Myeloma/N-cadherin (CD325)

  • N-cadherin blocking peptide, which completely disrupted interactions between N-cadherin on neoplastic cells with N-cadherin on stromal cells, induces widespread cell death in multiple myeloma cells
B-cell ALL/Fat1 cadherin

  • Overexpression of Fat1 cadherin in pediatric and adult B-ALL

  • High FAT1 mRNA expression associated with shorter relapse-free survival in pediatric B-ALL; Similar results were not observed in adult B-ALL or T-ALL

  • FAT1 is considered MRD marker since it is absent in hematopoietic progenitors

  • Mutations in FAT1 gene have been identified in different cancers including ALL.

  • Some FAT1 mutations in solid tumors prevented Fat1 cadherin binding to β-catenin resulting in deregulated activation of Wnt signaling pathway; the effect of these mutations in ALL is not characterized.
T-cell ALL/Fat1 cadherin

  • Overexpression of Fat1 cadherin in pediatric and adult T-ALL.
CLL/Fat1 cadherin

  • Fat1 cadherin mutated in fludarabine-resistant CLL samples