Methods for diagnosis, prognosis and methods of treatment
The present invention provides an approach for the determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, expression markers and other criteria, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of modulators of cellular activation allows for characterization of pathways and cell populations. Several exemplary diseases that can be analyzed using the invention include AML, MDS, and MPN.
1. A kit for determining whether or not an individual with AML will respond to treatment comprising
(i) an apoptosis-inducing agent selected from the group consisting of Staurosporine, Etoposide, Mylotarg, Daunorubicin, and AraC, and combinations thereof;
(ii) a binding element specific for a cell surface marker selected from the group consisting of CD34, CD33, CD45, HLADR, CD11B, FLT3 Ligand, c-KIT, ABCG2, MDR1, BCRP, MRP1, LRP, and combinations thereof; and
(iii) a state-specific binding element specific for an activatable element selected from the group consisting of PARP+, Cleaved Caspase 3, Cleaved Caspase 8, and Cytochrome C.
2. The kit of claim 1 comprising 2 apoptosis-inducing agents.
3. The kit of claim 2 wherein the two apoptosis-inducing agents comprise Daunorubicin and AraC.
4. The kit of claim 2 wherein the state-specific binding element specific for an activatable element comprises a state-specific binding element specific for PARP + .
5. The kit of claim 2 wherein the binding element specific for a cell surface marker comprises a binding element specific for CD45.
6. The kit of claim 1 comprising 2 binding elements specific for a cell surface marker.
7. The kit of claim 6 wherein the 2 binding elements comprise a first binding element specific for CD45 and a second binding element specific for CD34.
8. The kit of claim 1 further comprising instructions, information, software, reagents, or a combination thereof.
9. The kit of claim 1 wherein the apoptosis-inducing agent comprises etoposide.