Composition and method for treating a hematological malignancy

1. A method for inhibiting BCL9 expression in a population of B cells in a first subject, the method comprising administering to the first subject a therapeutically effective amount of an agent comprising an miR-30 polynucleotide, wherein the population of B cells have a higher amount of BCL9 RNA or protein than a corresponding population of B cells from a second subject and wherein the second subject does not have multiple myeloma.

2. The method of claim 1 , wherein the administration of the agent decreases the amount of BCL9 RNA or protein in the population of B cells.

3. The method of claim 1 , wherein the population of B cells are sensitive to inhibition of a Wnt signaling pathway.

4. The method of claim 1 , wherein the miR-30 polynucleotide comprises a ribonucleic acid.

5. The method of claim 1 , wherein the miR-30 polynucleotide comprises a deoxyribonucleic acid.

6. The method of claim 1 , wherein the miR-30 polynucleotide comprises one or more non-naturally occurring polynucleotides.

7. The method of claim 6 , wherein the non-naturally occurring nucleotide is a 2′-O-methyl oligoribonucleotide.

8. The method of claim 1 , wherein the miR-30 polynucleotide comprises a polynucleotide that hybridizes specifically to one or more sequence motifs selected from the group consisting of SEQ ID NOs: 33 and 34.

9. The method of claim 1 , wherein the miR-30 polynucleotide comprises a motif having the nucleic acid sequence of SEQ ID NO: 36.

10. The method of claim 1 , wherein the miR-30 polynucleotide comprises a polynucleotide comprising one or more sequences selected from the group consisting of SEQ ID NOs: 1-5.

11. The method of claim 1 , wherein the agent further comprises a nanoparticle.

12. The method of claim 1 , wherein the agent further comprises a lipid.

13. The method of claim 11 , wherein the nanoparticle is a lipid nanoparticle.

14. The method of claim 1 , wherein the agent further comprises a viral vector.

15. The method of claim 14 , wherein the viral vector is a lentiviral vector, an adenoviral vector, an adeno-associated viral vector, or a retroviral vector.

16. The method of claim 1 , wherein the agent further comprises a plasmid.

17. The method of claim 1 , wherein the agent is administered intravenously or subcutaneously.

18. The method of claim 1 , wherein the subject has or is at risk for monoclonal Gammopathy of Undetermined Significance (MGUS), smoldering myeloma, asymptomatic MM, or symptomatic MM.

19. The method of claim 18 , wherein the symptomatic MM is newly diagnosed MM.

20. The method of claim 18 , wherein the symptomatic MM is late stage relapsed/refractory MM.

21. The method of claim 1 , further comprising administering an additional anti-cancer therapy to the subject.

22. The method of claim 21 , wherein the additional anti-cancer therapy is selected from the group consisting of surgery, chemotherapy, radiation, hormone therapy, immunotherapy, and a combination thereof.

23. The method of claim 21 , wherein the additional anti-cancer therapy reduces bone absorption.

24. The method of claim 21 , wherein the additional anti-cancer therapy reduces osteoclast mediated bone resorption.

25. The method of claim 23 , wherein the additional anti-cancer therapy is a bisphosphonate.

26. The method of claim 1 , wherein the subject is a human.

27. A method of reducing proliferation, survival, migration, or colony formation ability of multiple myeloma cells in a subject with multiple myeloma, the method comprising administering to the subject a therapeutically effective amount of an agent comprising an miR-30 polynucleotide, wherein the multiple myeloma cells have a higher amount of BCL9 RNA or protein than normal plasma cells.

28. A method of inhibiting metastasis of multiple myeloma in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an agent comprising an miR-30 polynucleotide, wherein the multiple myeloma cells have a higher amount of BCL9 RNA or protein than normal plasma cells.

29. A method of treating a hematological malignancy in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an agent comprising an miR-30 polynucleotide, wherein the hematological malignant cells have a higher amount of BCL9 RNA or protein than normal hematological cells.

30. The method of claim 29 , wherein the hematological malignancy is selected from the group consisting of myelodysplastic syndrome, Hodgkin's lymphoma, chronic lymphocytic leukemia, and B cell lymphoma.

31. The method of claim 9 , wherein the miR-30 polynucleotide comprises insertion, deletion or substitution of one or more nucleotides in a sequence selected from the group consisting of SEQ ID NOs: 1-5.