Methods and compositions for inducing deregulation of EPHA7 and ERK phosphorylation in human acute leukemias
View Patent ↗Methods for assessing a pathological condition in a subject include measuring one or more markers where a difference is indicative of acute lymphoblastic leukemia (ALL) or a predisposition to ALL, uses and compositions are disclosed.
1. A composition comprising at least one agent that interferes with an acute lymphoblastic leukemia (ALL) response signaling pathway in at least one leukemic cell producing an ALL1/AF4 chimeric fusion protein, wherein the agent comprises:
an isolated or synthetic ALL1/AF4-specific siRNA which suppresses expression of an ALL1/AF4 chimeric fusion protein; and
an isolated or synthetic EphA7-specific siRNA which suppresses expression of EphA7.
2. The composition according to claim 1 , wherein the isolated or synthetic ALL1/AF4-specific siRNA is an SEMj siRNA.
3. The composition according to claim 1 , wherein the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA.
4. The composition according to claim 1 , wherein the isolated or synthetic EphA7-specific siRNA is an siEphA7#2 siRNA.
5. The composition according to claim 1 , wherein the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA and an siEphA7#2 siRNA.
6. The composition according to claim 1 , further comprising: 5-iodotubercidin.
7. The composition according to claim 1 , wherein the agent is a-synthetic ALL1/AF4-specific siRNA, and a synthetic EphA7-specific siRNA.
8. The composition according to claim 1 , wherein the isolated or synthetic ALL1/AF4-specific siRNA is an SEMj siRNA, and the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA, an siEphA7#2 siRNA, or a combination thereof.
9. The composition according to claim 1 , wherein the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA, an siEphA7#2 siRNA, or a combination thereof.
10. The composition according to claim 1 , wherein at least two isolated or synthetic EphA7-specific siRNA targets EphA7 mRNA at two distinct regions.
11. The composition according to claim 10 , wherein the isolated or synthetic ALL1/AF4-specific siRNA is an SEMj siRNA, and the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA, an siEphA7#2 siRNA, or a combination thereof.
12. The composition according to claim 1 , wherein the leukemic cell is at least one leukemic cell selected from the group consisting of a K562 leukemic cell transfected with an ALL1/AF4 chimeric fusion protein construct; a pro-B leukemic SEMK2 cell having a t(4; 11) chromosome translocation; and a pro-B leukemic RS4 cell having a t(4; 11) chromosome translocation.