Transcriptomic analysis of hyperglycemic stress induced myeloid neoplasms associated with Tet2 haploinsufficiency

Purpose: To identify potential mediators of myeloid neoplasms driven by Tet2 haploinsufficiency and hyperglycemic stress. Methods: Lin-negative bone marrow cells from WT, Tet2+/-, Ins2Akita/+ and Tet2+/-;Ins2Akita/+ were used for total RNA purification and RNA-seq. Results: Using unbiased Gene Set Enrichment Analysis (GSEA), we identified that innate immune pathway, IL-6 signaling pathway and TLR4-NFkB pathway were significantly enriched in the compound mutants (Tet2+/-;Ins2Akita/+) while controls (Tet2+/- or Ins2Akita/+) were similar to WT mice. Bone marrow Lin-negative RNA profile in four genotypes: WT, Tet2+/-, Ins2Akita/+ and Tet2+/-;Ins2Akita/+.