[Study on the Relationship between Integrin 2A and Drug Resistance in Chronic Myeloid Leukemia].

OBJECTIVE

To explore the expression pattern and clinical significance of Integral membrane protein 2A（ITM2A） in drug resistant patients with chronic myeloid leukemia (CML).

METHODS

The expression of ITM2A in CML was evaluated by qRT-PCR, Western blot and immunocytochemistry. In order to understand the possible biological effects of ITM2A, apoptosis, cell cycle and myeloid differentiation antigen expression of CML cells were detected by flow cytometry after over-expression of ITM2A. The nuderlying molecular mechanism of its biological effect was explored.

RESULTS

The expression of ITM2A in bone marrow of CML resistant patients was significantly lower than that of sensitive patients and healthy donors（P<0.05）. The CML resistant strain cell K562R was successfully constructed in vitro. The expression of ITM2A in the resistant strain was significantly lower than that in the sensitive strain(P<0.05). Overexpression of ITM2A in K562R cells increased the sensitivity of K562R cells to imatinib and blocked the cell cycle in G2 phase(P<0.05), but did not affect myeloid differentiation. Mechanistically, up-regulation of ITM2A reduced phosphorylation in ERK signaling (P<0.05).

CONCLUSION

The expression of ITM2A was low in patients with drug resistance of CML, and the low expression of ITM2A may be the key factor of imatinib resistance in CML.