Our model predicts that patients who have low MDR activity and a high CD33 production rates are most likely to benefit from GO. These two parameters can be evaluated LEE011 cost relatively easily by flow cytometry, after in vitro exposure of blast cells to GO. Our findings further suggest that GO efficacy could be enhanced when used after the leukemic tumor burden was modestly lowered, e.g by alternative cyto-reductive agents. Model predictions suggest that the second GO dose should not be administered before day 7, which is corroborated by comparison with data from prospective randomized trial of GO in elderly AML patients. We suggest that incorporation of our results in clinical practice can serve identification of the subpopulation of elderly patients who can benefit most of the GO treatment and enable return of the currently suspended drug to clinical armamentarium of hematologists. Heart formation is one of the earliest morphogenic events during animal development. The development of the heart is under the control of a complex transcriptional network, and dysregulation of the expression or genetic mutation of cardiac genes often leads to abnormality in the morphology and the function of the heart. Congenital heart defects are found in more than 1% life birth in human beings and are the most common diseases affecting children. One type of CHD, the Holt-Oram syndrome occurs in a frequency of 1 of 100,000 with defects in the heart and upper limbs. Mutations of Tbx5, a member of the T-box family of transcription factors, have been identified as a causative gene of the HOS. The Tbx5 mutations found from the HOS patients include missense mutations, deletions that induce open reading frame shifts, and premature truncations. Whereas haploinsufficiency of Tbx5 in transgenic mice mimics the HOS, homologous deletion of the Tbx5 gene led to early embryonic lethality. The fact that deletion of only one copy of the Tbx5 genomic sequence already resulted in defects in the mouse model further suggested that the dosage of the Tbx5 gene is critical for the development of the heart and the expression of Tbx5 downstream genes. Consistent with this view, overexpression of Tbx5 under the b-myosin heavy chain promoter in embryonic mouse hearts led to a failure of ventricular development and embryonic lethality in mice. Overexpression of Tbx5 via gene duplication severely affects the development of the heart and limbs in human patients. Furthermore, carriers of Tbx5 mutations show different levels of impairments on the development of the heart and limbs on an individual basis and it was observed that the severity of defects varies even between patients with the same genetic background. Intriguingly, it was also noticed that some Tbx5 mutations lead to more severe abnormity than others. However, the molecular mechanisms underlying those observations are not fully understood. Tbx5 cooperates with other transcriptional factors to regulate the expression of its target genes. Tbx5 has been shown to interact with Nkx2.5, GATA4, Mef2c, Sall4 and TAZ to synergistically activate target genes expression in cardiomyocytes.