Compositions and methods for treating chronic myelomonocytic leukemia
View Patent ↗As disclosed herein, the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed and prognostic in Chronic Myelomonocytic Leukemia (CMML). MALAT1 depletion is disclosed herein as therapeutic strategy for treating CMML and other MALAT1 overexpressing leukemias. Also disclosed herein is a method of treating a subject with a leukemia that involves co-administering to the subject a MALAT1 silencing agent and a therapeutically effective amount of a differentiation agent, such as all-trans retinoic acid (ATRA).
1 . A method for treating chronic myelomonocytic leukemia (CMML) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a MALAT1 antisense oligonucleotide or siRNA and a therapeutically effective amount of retinoic acid, wherein the MALAT1 antisense oligonucleotide or siRNA comprises a nucleic acid sequence that is complementary to a contiguous portion of human MALAT1 RNA 14 to 100 base pairs in length.
2 . The method of claim 1 , wherein the retinoic acid comprises all-trans retinoic acid (ATRA).
3 . The method of claim 1 , further comprising administering to the subject a therapeutically effective amount of dexamethasone.
4 . The method of claim 1 , wherein the subject has not received dexamethasone.
5 . A composition, comprising a therapeutically effective amount of a MALAT1 antisense oligonucleotide or siRNA and a therapeutically effective amount of retinoic acid, wherein the MALAT1 antisense oligonucleotide or siRNA is complementary to a contiguous portion of human MALAT1 RNA 14 to 100 base pairs in length.
6 . The composition of claim 5 , wherein the retinoic acid comprises all-trans retinoic acid (ATRA).
7 . The composition of claim 5 , further comprising a therapeutically effective amount of dexamethasone.