UC Merced

Hematopoiesis depends on complex interactions between hematopoietic stem cells (HSCs) and the bone marrow (BM) microenvironment. However, alterations in this regulated system can lead to malignant transformation and hematopoietic diseases. Acute myeloid leukemia (AML) is characterized by uncontrolled growth of leukemic blasts in the BM and is the most common acute leukemia in adults. Tumor survival after cytotoxic treatment of AML patients remains a major therapeutic challenge, contributing to disease relapse. Fine-tuning the cytotoxic conditioning regimen to discover the most effective treatment plan has the potential to significantly improve outcomes in AML patients, thereby reducing the risk of relapse. The mechanism by which conditioning achieves therapeutic outcomes is through BM ablation. Additionally, conditioning can impact different compartments of the BM microenvironment. In this study, we investigated the impact of busulfan conditioning on the BM niche, focusing on how the intensity of cytotoxic conditioning regimens and animal age influence this dynamic process. We later expanded our findings to an AML mouse model to evaluate the BM niche around resistant tumor cells after cytotoxic therapy.

By examining the impact of varying dosages and recipient age factors on treatment response as well as BM microenvironment adjacent to the residual tumor cells after therapy, we sought to optimize chemotherapy regimens and establish the groundwork for tailoring treatment strategies to AML cancer patients.