Hematopoietic stem cells (HSCs) are tissue-specific cells giving rise to all mature blood cell types regulated by a diverse group of hematopoietic cytokines and growth factors that influences the survival & proliferation of early progenitors and differentiation mechanisms by modulating the functional activities of HSCs. In this study, the functional yet distinctive role of three novel combinations of gene pairs RRAGC & PSMC2;CKAP4 & MANF;and CTR9 & CNTNAP2 have been newly identified. These novel combinations of genes were confirmed and expressed in K562 human leukemic cell line in the presence of cytokine combination (IL-3, FLT-3 and SCF) using RT-PCR and siRNA-mediated gene knock down strategy. This study signifies the synergistic role of gene pairs in different molecular activities like ubiquitination or proteasomal degradation, calcium mobilization, dopamine signaling.