Role of N-cadherin in MSC-mediated protection of CML stem/progenitor cells from TKI treatment. (A) CML CD34⁺ cells cocultured on MSCs without IM (left) and with IM (right) adhered to and migrated underneath (right, arrowhead) MSCs. (B) The fraction of MSC-adherent CML CD34⁺ cells with or without IM. (C) Representative flow cytometry plots and (D) graphs showing apoptosis of CML CD34⁺ cells (C) and CD34⁺CD38⁺ and CD34⁺CD38⁻ cells (D) cultured without MSCs in a Transwell insert above MSC layers or in contact with MSCs in the absence or presence of IM (n = 3). (E) Representative flow cytometry plots showing N-cadherin expression on CML and normal CD34⁺, CD34⁺CD38⁻, and CD34⁺CD38⁺ cells. (F) N-cadherin mRNA levels in CML and normal CD34⁺CD38⁻ and CD34⁺CD38⁺ cells (n = 3 CML patients and 3 healthy controls). (G) Representative flow cytometry plots showing N-cadherin expression on CML CD34⁺ cells cultured with and without IM and with or without MSCs. (H) N-cadherin mRNA levels in CML CD34⁺ cells cultured with and without IM in the presence or absence of MSCs (left), in adherent (adh) and nonadherent suspension (susp) cells, and in cells treated with an N-cadherin blocking (NCDH) and NCDH control peptide (right) (n = 3). (I) Reduced adhesion of CML CD34⁺ cells to MSCs in the presence of NCDH peptides. (J) Apoptosis of IM-treated CML CD34⁺ cells cocultured with MSCs in the presence of NCDH or control peptides (n = 3). (K) Apoptosis of IM-treated CML CD34⁺CD38⁻ and CD34⁺CD38⁺ cells cocultured with MSCs and N-cadherin blocking or isotype control antibodies (n = 3). ns, not significant. *P < .05; **P < .01.