Leukemia is the most common type encountered in pediatric and adult patients. In acute leukemia, Hematopoietic Stem Cells (HSCs) reside in specialized niche in the Bone Marrow (BM). These stem cells are thought to provide signals that support key HSC properties. Normality, cytokines regulate a variety of hematopoietic cell functions through the activation of multiple signal transduction pathways. In this regard, regulation of proliferation and differentiation of HSCs is related by the gene expression pattern in the cell and the composition of external signals from the BM niche. Transcription factors regulate express of gene, meanwhile external signals can be mediated by cellcell interactions, cell- extracellular matrix interactions and growth factors as well which may promote proliferation, differentiation, migration and apoptosis. Moreover, HSCs are multipotent stem cells defined by their ability to selfrenewal, differentiation and maintenance of all blood cell types in hematological system. These properties make HSCs like other tissue stem cells, prime targets for malignant transformation. Also we know, molecular advances of acute leukemia have led to discovery of numerous additional changes including mutation involving key cellular pathways in myeloid and lymphoid development, tumor suppression, and cell cycle regulation as well. Hence, I want to explain concerning genetic basis of acute leukemia particularly in Acute Lymphoblastic Leukemia (ALL), HSCs source as well, also malignant and nonmalignant hematopoietic progenitor cells.