Leukemia stem cells (LSCs) are responsible for therapeutic failure and relapse of acute lymphoblastic leukemia. As a result of the interplay between LSCs and bone marrow mesenchymal stem cells (BM-MSCs), cancer cells may escape from chemotherapy and immune surveillance, thereby promoting leukemia progress and relapse. The present study identified that the crosstalk between LSCs and BM-MSCs may contribute to changes of immune phenotypes and expression of hematopoietic factors in BM-MSCs. Furthermore, Illumina Genome Analyzer/Hiseq 2000 identified 7 differentially expressed genes between BM-MSCsLSC and BM-MSCs. The Illumina sequencing results were further validated by reverse transcription-quantitative polymerase chain reaction. Following LSC simulation, 2 genes were significantly upregulated, whereas the remaining 2 genes were significantly downregulated in MSCs. The most remarkable changes were identified in the expression levels of lumican (LUM) gene. These results were confirmed by western blot analysis. In addition, decreased LUM expression led to decreased apoptosis, and promoted chemoresistance to VP-16 in Nalm-6 cells. These results suggest that downregulation of LUM expression in BM-MSCs contribute to the anti-apoptotic properties and resistance to chemotherapy in LSCs.Keywords: Illumina sequencing; acute lymphoblastic leukemia; bone marrow mesenchymal stem cells; leukemia stem cell; lumican.