Previous studies have demonstrated that 32D cells expressing TrkA grow and survive in IL 3 lowered culture conditions, along with display increased levels of phosphorylation of Y490 on p AKT and TrkA, p ERK1/2 and cause AML in mice. In our studies, we observed that therapy with 17 DMAG induced much more angiogenesis pathway apoptosis of 32D cells expressing either wild type TrkA or TrkA than 32D cells transfected with vector alone. We next determined the effects 17 DMAG and/or TrkA particular signaling chemical K 252a in human leukemia cells. Treatment with K 252a induces a dose-dependent escalation in apoptosis of TF 1 greater than K562 cells, as shown in Figure 3C. We then determined the effect of inhibiting TrkA signaling in K562 cand 32D/wtTrkA cells. while exposure to K 252a inhibited NGF induced g TrkA levels, as previously described, company treatment with 17 DMAG and E 252a produced further fall in the NGF induced phosphorylation of TrkA. An identical result of E 252a corp treatment and 17 DMAG was also seen on p AKT degrees. Consistent with these findings, combined treatment with E 252a and 17 DMAG applied a superior anti apoptotic result against K562 cells.. Investigation of the dose effect partnership for 17 DMAG and E 252a in K562 cells was done based on the mean Urogenital pelvic malignancy dose effect method of Talalay and Chou. After this, the combination index values were calculated using the web apoptotic cells by the co treatment of both agents. The mixed treatment of 17 DMAG and E 252a results in a synergistic increase in the fraction of apoptotic cells with the CI values ranging from 0, as could be observed. 8 to 0. 4, respectively. These findings suggest that, as compared to each agent alone, co treatment with 1 and E 252a DMAG more potently abrogates TrkA mediated survival signaling and induces cell death of human leukemia cells. Co culture with NGF created by these cells and the HS 5 BMSC has been proven to promote survival of TrkA expressing leukemia cells. We next established whether 17 DMAG could induce apoptosis of leukemia cells company classy with Gemcitabine HS 5 cells. Our findings show that 17 DMAG therapy caused comparable rate of apoptosis in K562 cells with or without company tradition with HS 5 cells. PC 12 cells separate and form neurites following experience of TrkA and NGF induced signaling. We next determined the effect of 17 DMAG on TrkA degrees and NGF mediated neurite formation and differentiation in PC12 cells. Treatment with 17 DMAG measure dependently reduced the levels of TrkA with concomitant fall in c Raf levels, a known hsp90 client protein, as shown in Figure 5A. Furthermore, treatment with 17 DMAG inhibited NGF induced neurite development and differentiation of PC 12 cells.