MBD2 Ablation Impairs Lymphopoiesis and Impedes Progression and Maintenance of T-cell Acute Lymphoblastic Leukemia

Little is known about the roles of methyl-CpG-binding domain protein 2 (MBD2), a “reader” of DNA methylation, in T-cell acute lymphoblastic leukemia (T-ALL). Here, we investigated the role of MBD2 in T-ALL by using an Mbd2 knockout mouse model. We found that MBD2 ablation impeded the progression and maintenance of Notch1-driven T-ALL.Our data reveals essential roles for MBD2 in lymphopoiesis and T-ALL and support an intriguing potential of MBD2 as a therapeutic target for T-ALL. To explore potential mechanisms underlying the anti-ALL effects of MBD2 ablation, leukemic cells were harvested from mice transplanted with WT or Mbd2-/- T-ALL cells, and their global gene expression profiles (GEP) were compared. Double positive (DP) thymocytes were isolated and used as a normal control. To understand the critical molecular events caused by MBD2 ablation in Notch1-driven T-ALL,the GFP+ leukemic mice BM cells were sorted from the recipients of MBD2-/- (TALL_M1,TALL_M2,TALL_M3) or MBD2+/+ (TALL_C1,TALL_C2,TALL_C3), and subjected to microarray analysis on Affymetrix microarrays.Furthermore, the normal DP (double positive) cells from steady-state mice thymus were chosen for examination as the other control groups.The DP cells were sorted from thymus of MBD2-/- (DP_M1,DP_M2,DP_M3) or MBD2+/+ (DP_C1,DP_C2,DP_C3) mice, and subjected to microarray analysis on Affymetrix microarrays.