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 method to interfere with an acute lymphoblastic leukemia (ALL) response signaling pathway in at least one leukemic cell producing an ALL1/AF9 chimeric fusion protein, wherein the method comprises:
administering, to at least one leukemic cell, an ALL1/AF9-specific siRNA which suppresses expression of an ALL1/AF9 chimeric fusion protein, thereby interfering with an acute lymphoblastic leukemia (ALL) response signaling pathway; and,
administering at least one EphA7-specific siRNA.
2. The method of claim 1 , wherein the at least one leukemic cell further comprises a living organism.
3. The method of claim 2 , wherein the organism is a human.
4. The method of claim 1 , wherein the at least one leukemic cell is selected from the group consisting of: a K562 leukemic cell transfected with an ALL1/AF9 chimeric fusion protein construct; a pro-B leukemic SEMK2 cell having a t(9; 11) chromosome translocation; and a pro-B leukemic RS4 cell having a t(9; 11) chromosome translocation.
5. A method to interfere with an acute lymphoblastic leukemia (ALL) response signaling pathway in at least one leukemic cell producing an ALL1/AF9 chimeric fusion protein, wherein the method comprises:
administering, to at least one leukemic cell, an ALL1/AF9-specific siRNA which suppresses expression of an ALL1/AF9 chimeric fusion protein, thereby interfering with an acute lymphoblastic leukemia (ALL) response signaling pathway; and,
administering 5-iodotubercidin to the leukemic cell.
6. The method of claim 1 , wherein the ALL1/AF9-specific siRNA is a SEMj siRNA.
7. A method of inducing apoptosis in, and/or suppressing growth of, at least one leukemic cell producing an ALL1/AF4 chimeric fusion protein, wherein the method comprises:
suppressing expression of an ALL1/AF4 chimeric fusion protein in the leukemic cell by treating the leukemic cell with an ALL1/AF4-specific siRNA; and
suppressing expression of EphA7 in the leukemic cell by treating the leukemic cell with an EphA7-specific siRNA.
8. The method of claim 7 , further comprising: inhibiting Erk1/2 phosphorylation in the leukemic cell by treating the leukemic cell with 5-iodotubercidin.
9. The method of claim 7 , wherein the ALL1/AF4-specific siRNA is an SEMj siRNA.
10. The method of claim 7 , wherein the EphA7-specific siRNA is an siEphA7#1 siRNA.
11. The method of claim 7 , wherein the EphA7-specific siRNA is an siEphA7#2 siRNA.
12. The method of claim 7 , wherein at least two EphA7-specific siRNA target EphA7 mRNA at two distinct regions.
13. The method of claim 5 , wherein the at least one leukemia cell further comprises a living organism.
14. The method of claim 13 , wherein the living organism is a human.
15. The method of claim 5 , wherein the at least one leukemic cell is selected from the group consisting of: a K562 leukemic cell transfected with an ALL1/AF9 chimeric fusion protein construct; a pro-B leukemic SEMK2 cell having a t(9; 11) chromosome translocation; and a pro-B leukemic RS4 cell having a t(9; 11) chromosome translocation.
16. The method of claim 1 , wherein the ALL1/AF9-specific siRNA is a SEMj siRNA.