Leukemia is the most common type encountered in pediatric and adult ƉĂƟĞnƚƐ͘ In acute leukemia, ,ĞmĂƚŽƉŽŝĞƟc Stem Cells (HSCs) reside in specialized niche in the Bone Marrow (BM). These stem cells are thought to provide signals that support key HSC ƉrŽƉĞrƟĞƐ͘ Normality, cytokines regulate a variety of ŚĞmĂƚŽƉŽŝĞƟc cell ĨƵncƟŽnƐ through the ĂcƟǀĂƟŽn of mƵůƟƉůĞ signal ƚrĂnƐĚƵcƟŽn pathways. In this regard, rĞŐƵůĂƟŽn of ƉrŽůŝĨĞrĂƟŽn and ĚŝīĞrĞnƟĂƟŽn of HSCs is related by the gene expression ƉĂƩĞrn in the cell and the cŽmƉŽƐŝƟŽn of external signals from the BM niche. drĂnƐcrŝƉƟŽn factors regulate express of gene, meanwhile external signals can be mediated by cellcell ŝnƚĞrĂcƟŽnƐ͕ cell- extracellular matrix ŝnƚĞrĂcƟŽnƐ and growth factors as well which may promote ƉrŽůŝĨĞrĂƟŽn͕ ĚŝīĞrĞnƟĂƟŽn͕ mŝŐrĂƟŽn and apoptosis. Moreover, HSCs are mƵůƟƉŽƚĞnƚ stem cells ĚĞĮnĞĚ by their ability to selfrenewal, ĚŝīĞrĞnƟĂƟŽn and maintenance of all blood cell types in hematological system. These ƉrŽƉĞrƟĞƐ make HSCs like other ƟƐƐƵĞ stem cells, prime targets for malignant ƚrĂnƐĨŽrmĂƟŽn͘ Also we know, molecular advances of acute leukemia have led to discovery of numerous ĂĚĚŝƟŽnĂů changes including mƵƚĂƟŽn involving key cellular pathways in myeloid and lymphoid development, tumor suppression, and cell cycle rĞŐƵůĂƟŽn as well. Hence, I want to explain concerning ŐĞnĞƟc basis of acute leukemia ƉĂrƟcƵůĂrůy in Acute >ymƉŚŽbůĂƐƟc Leukemia (ALL), HSCs source as well, also malignant and nonmalignant ŚĞmĂƚŽƉŽŝĞƟc progenitor cells.