Methods for treating, diagnosing and prognosing a haematological malignancy
View Patent ↗The invention relates to a serotonin receptor (5-HTR) inhibitor selected from the group consisting of a type 1 5-HTR inhibitor and a type 2 5-HTR inhibitor for use in the prevention and/or treatment of a haematological malignancy. Additionally, the invention relates to in vitro methods for the identification or isolation of a malignant cell from a haematological malignancy or for diagnosing a haematological malignancy based on detecting the expression of type 1 5-HTR and/or type 2 5-HTR. Furthermore, the invention relates to in vitro methods for determining the prognosis, for monitoring the effect of a therapy or for designing a customized therapy in a subject suffering from a haematological malignancy based on determining the levels of type 1 5-HTR and/or type 2 5-HTR.
1. A method of inducing cell death in a haematological malignancy cell thereof comprising contacting the cell with an effective amount of apomorphine or a pharmaceutically acceptable salt thereof, or a combination thereof, wherein binding of the apomorphine, pharmaceutically acceptable salt thereof, or combination thereof to a 5-hydroxytryptamine receptor (5-HTR) expressed on the surface of the cell induces cell death on the hematological malignancy cell.
2. The method of claim 1 , wherein the haematological malignancy is of myeloid lineage.
3. The method of claim 2 , wherein the haematological malignancy of myeloid lineage is acute myeloid leukemia (AML).
4. The method of claim 2 , wherein the haematological malignancy of myeloid lineage is myeloid lineage is acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome, chronic myelogenous leukaemia (CML) or acute monocytic leukaemia (AMoL).
5. The method of claim 1 , wherein the heamatological malignancy is of lymphoid lineage.
6. The method of claim 5 , wherein the haematological malignancy of lymphoid lineage is acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), a Hodgkin's lymphoma, a non-Hodgkin's lymphoma, or a myeloma.
7. The method according to claim 1 , wherein said method further comprises measuring the expression levels of 5-HTR in the malignant cells of a sample obtained from the subject, wherein the presence of 5-HTR in the malignant cell indicates that the malignant cell is suitable for treatment with apomorphine.
8. The method of claim 7 , wherein the sample is selected from the group consisting of bone marrow, blood, and lymph nodes.
9. The method of claim 8 , wherein the blood is peripheral blood.
10. The method of claim 7 , wherein the expression level of 5-HTR in the malignant cell is determined by measuring the level of mRNA encoded by the 5-HTR genes.
11. The method of claim 7 , wherein the expression level of 5-HTR is determined by measuring the level of 5-HTR proteins or variants thereof.
12. The method of claim 10 , wherein the level of mRNA encoded by the 5-HTR genes is determined by PCR.
13. The method of claim 11 , wherein the level of 5-HTR proteins or variants thereof is determined by Western blot or immunocytochemistry.
14. The method according to claim 7 , wherein said method further comprises comparing the expression levels of 5-HTR in the cells of the sample with a reference value, wherein
(a) a decrease of the expression level of 5-HTR with respect to the reference value is indicative that the subject shows a good prognosis; and,
(b) an increase of the expression level of 5-HTR with respect to the reference value is indicative that the subject shows a bad prognosis; and,
wherein the therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt thereof, or a combination thereof, is administered to the subject if the subject shows a bad prognosis.
15. The method of claim 1 , wherein the 5-HTR is type 1 5-HTR, type 2 5-HTR, or a combination thereof.