Background and purpose: The key component of the hematopoietic microenvironment is bone marrow stromal cells (BMSC). Several studies have provided evidence suggesting that proliferation

survival

and drug resistance of AML can be modulated by BMSC within the bone marrow hematopoietic microenvironment. Therefore

in addition to therapies that directly target acute myelogenous leukemia (AML)

interruption of leukemia cell and BMSC interactions should be considered when designing anti-AML therapeutic strategies. Hedgehog (Hh) protein belongs to a family of secreted proteins

which is widely expressed in mammals and non-mammals species and involved in the regulation of a variety of tumor formation in mature organs

angiogenesis

stem cell differentiation

immune cells

and embryonic development. Hh signaling allows for the modulation of the microenvironment to prepare a tumor-suitable niche by manipulating tumor cell growth

differentiation

and immune regulation

thus creating an enabling environment for progression and metastasis. However

it remains unclear whether the bone marrow hematopoietic microenvironment contributes to the increased survival of HL-60 cells by Hh signaling. Therefore

we studied the influence of bone marrow stromal cell-induced Hh signaling on the survival of HL-60 cells. Methods: CCK-8 kit was used for the detection of HL-60 cell proliferation in different experimental groups. Annexin V-FITC/PI double staining was used to detect the HL-60 cell apoptotic rate. Semiquantitative reverse transcription polymerase chain reaction (SQRT-PCR) was used to detect the experimental group Hh signaling pathway components of GLI1 mRNA and BCL-2

BCL-XL expression. GLI1 apoptotic gene expression levels were measured using immunofluorescence assay. Results: Bone marrow stromal cells promote proliferation and inhibit apoptosis of HL-60 cells

and 10 μmol/L of GANT61 can reverse these effects of bone marrow stromal cells. In co-culture system of HL-60 cells

GLI1 protein and mRNA expression increased and apoptosis inhibiting gene expression of BCL-2 and BCL-XL mRNA were upregulated. Conclusion: Bone marrow stromal cells have a protective effect on acute myeloid leukemia cells. The mechanism may involve activation of the Hh signaling pathway in acute myeloid leukemia cells by bone marrow stromal cells leading to increased expression of downstream target gene BCL-2 and BCL-XL.