INTRODUCTION: The current understanding highlights the intricate relationship between leukemic cells and their microenvironment, emphasizing the significant impact of environmental factors on chemotherapy resistance or sensitivity. Platelet-derived microparticles (PMPs) play a crucial role in facilitating intercellular communication, significantly contributing to the complex dynamics of cancer pathology and treatment outcomes. This study aims to investigate the cytotoxic and apoptotic effects of PMP, Ara-C, and their combinations on cancer cells, as well as their influence on the expression of critical genes like Bax, Bcl-2, P21, and h-TERT in the context of Acute Lymphoblastic Leukemia (ALL) cell line (Nalm-6). METHODS: PMPs were isolated through centrifugation at varying speeds, and their concentration was determined using the BCA assay. The size and immunophenotypic characteristics of PMPs were analyzed using dynamic light scattering (DLS) and flow cytometry. The cytotoxic and apoptotic effects of PMP, Ara-C, and their combinations on Nalm-6 cells were assessed using the MTT assay, the trypan blue exclusion assay, and flow cytometry. Gene expression levels were analyzed using real-time PCR. RESULTS: According to our research findings, PMPs did not independently impact the viability and apoptosis of Nalm-6 cells; however, they synergistically augmented Ara-C's suppressive impact on viability and apoptosis. The MTT assay showed that both PMPs and Ara-C, whether administered alone or in combination, had a cytotoxic effect on the Nalm-6 cells. Furthermore, the combined treatment significantly affected the expression of Bax, Bcl-2, P21, and h-TERT genes. CONCLUSION: Our study demonstrates that PMPs have the potential to improve the effectiveness of Ara-C chemotherapy in treating ALL. These findings contribute to a deeper understanding of the interplay between PMP and chemotherapy agents, offering potential insights for optimizing treatment strategies and improving patient outcomes in ALL.