Abstract
Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However, there are certain differences in biology between CML and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Little is known about the role and mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study co-cultured hBMSCs with the TKI-resistant SUP-B15. Next, the proliferation of SUP-B15 was detected using a Cell Counting Kit-8. Additionally, quantitative polymerase chain reaction and flow cytometry were used to detect the expression of the associated genes and proteins. The present study explores the role and mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study showed that hBMSCs promoted the proliferation of TKI-resistant Ph+ ALL. This was shown by the increase in cells in the S+G2-M phase of the cell cycle. It was also found that the expression of cyclins A, C, D1 and E was increased. Apoptosis was inhibited through upregulation of anti-apoptotic genes [B-cell lymphoma-2 (BCL-2) and BCL-extra large] and downregulation of apoptotic genes (BCL-XS, BCL-2-associated X protein, and caspases 3, 7 and 9). Expression of the breakpoint cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL) gene, Wnt5a, and Wnt signaling pathway-associated genes (glycogen synthase kinase-3β, β-catenin, E-cadherin and phosphoinositide 3-kinase) and transcription factors (c-myc, ephrin type-B2, fibroblast growth factor 20 and matrix metalloproteinase 7) was also increased. Furthermore, the expression of drug resistance genes (low-density lipoprotein receptor, multidrug resistance-associated protein and multi-drug resistance gene) was increased and the expression of anti-oncogenes (death-associated protein kinase and interferon regulatory factor-1) was decreased. It was concluded that hBMSCs promote the growth of TKI-resistant Ph+ ALL by these aforementioned mechanisms. Therefore, targeting hBMSCs may be a promising approach for preventing the growth of TKI-resistant Ph+ ALL.