 Plan: The expression data of pre-treatment as well as the 1-week and 1-month after initiation of treatment samples is retrieved from SMD. The two class paired SAM analysis is performed to compare pre-treatment samples with samples collected at either 1-week or 1-month after initiation of treatment in responders and non-responders. The two class unpaired SAM analysis is also used to compare post-treatment samples of responders and non-responders at the same time point. The significant genes q value0.05, fold change2.5 are subsequently analyzed by IPA Ingenuity Pathway Analysis system to be transformed into a set of relevant networks based on the extensive records maintained in the Ingenuity Pathway Knowledge Base. The statistically significant networks, molecular and cellular functions, top canonical pathways and toxicity lists associated with each pair of dataset will be recognized through this analysis. Hypothesis on non-response to TPO mimetics can be generated based on the different functional subsets of significant genes. Genes involved in important pathways identified by IPA analysis will be validated by QRT-PCR as in our recent publication on oxidative stress pathways in ITP4. Our goal is to develop biomarkers which predict likelihood of response to therapy and identify pathways associated with resistance to therapy which could be targeted. 