Myeloid differentiation program

The myeloid differentiation program is a complex, highly regulated biological process involving the sequential activation and repression of specific gene sets that guide hematopoietic stem cells (HSCs) toward mature myeloid lineages, such as neutrophils, monocytes, and macrophages (Lian et al., 2001). This program is orchestrated by a network of master transcription factors, including PU.1, C/EBPα, and GFI1, which coordinate the transition from multipotent progenitors to terminally differentiated cells (Frontiers in Oncology, 2021). In many hematological malignancies, particularly acute myeloid leukemia (AML), this differentiation program is pathologically arrested at an immature blast stage due to genetic mutations or epigenetic alterations (NIH, 2021). Therapeutic strategies known as differentiation therapy aim to bypass or reverse this block, re-activating the myeloid differentiation program to induce the maturation and subsequent apoptosis of malignant cells (Blood, 2001). Drugs such as all-trans retinoic acid (ATRA) and IDH inhibitors have successfully demonstrated the clinical utility of targeting the pathways that control this program, transforming the treatment landscape for specific leukemia subtypes (NIH, 2022).

Other names

Myeloid maturation programMyeloid gene expression programMyeloid developmental programDifferentiation program

Induction of terminal differentiation in leukemic blasts by overcoming the differentiation block through various molecular mechanisms, such as retinoic acid receptor alpha (RARα) activation, isocitrate dehydrogenase (IDH) inhibition, or lysine-specific demethylase 1 (LSD1) inhibition.