Differences of HLA Gene Regulatory Network in Human Myeloid and Lymphoid Leukemias

Down-regulation of cell surface expression of Human Leukocytic Antigens (HLA) is the most important strategy that is being adapted by cancer cells against immune attack. Both classes of HLA, class I and class II are reported to be down-regulated in different cancers and leukemia is of no exception. HLA promoter sequences reveal that HLA class I expression is regulated by two modes - constitutive and inducible; while HLA class II is regulated by later mode only. Regulation of both constitutive and inducible expression are governed by different transcription factors (TFs). Using 1
^st
order information theory based analysis for HLA class I and its associated TFs (human) gene expression data reveals that RFXB, an inducible controlling TF plays a major role in different leukemias having myeloid and/or lymphoid origin; however, in lymphoid leukemia CREB1, another inducible TF may play an important role. Application of multivariate dependence information theory for MaxEnt analysis confirms the same finding. Moreover, this analysis reveals that another combination of two TFs namely CIITA and IRF1 have a significance in myeloid leukemic cells only; however no alteration is observed for other combinations of TFs in either HLA class II gene regulation or leukemia of lymphoid origin.