Methods for treating, diagnosing and prognosing a haematological malignancy

Abstract

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 - 34 . (canceled) 
     
     
         35 . A method of treating a subject suffering from acute myeloid leukemia (AML) comprising determining the expression of type 1B serotonin receptor (5-HTR 1B) in AML cells, wherein an administration of a 5-HTR 1B inhibitor to the subject induces cell death in the AML cells if the AML cells express 5-HTR 1B. 
     
     
         36 . The method of  claim 35 , wherein the 5-HTR 1B inhibitor is selected from the group consisting of methiothepin, alprenolol, AR-A000002, asenapine, cynipindolol, GR-127,935, iodocyanopindolol, isamoltane, metergoline, oxprenolol, pindolol, propranolol, SN-216,641, yohimbine, GR-55562, SB-224289, SB-236057, and a pharmaceutically acceptable salt thereof. 
     
     
         37 . The method of  claim 35 , wherein the expression of 5-HTR 1B in AML cells is detected by measuring the level of 5-HTR 1B proteins. 
     
     
         38 . The method of  claim 35 , wherein the expression of 5-HTR 1B in AML cells is detected by measuring the level of mRNA encoded by 5-HTR 1B genes. 
     
     
         39 . The method of  claim 37 , wherein the expression level of 5-HTR 1B proteins is determined by Western blot or immunocytochemistry. 
     
     
         40 . The method of  claim 38 , wherein the expression level of 5-HTR 1B genes is determined by PCR. 
     
     
         41 . The method of  claim 37 , wherein the expression of 5-HTR 1B is determined a blood sample. 
     
     
         42 . The method of  claim 41 , wherein the blood sample is a peripheral blood sample. 
     
     
         43 . A method of monitoring and treating a subject suffering from AML comprising:
 (a) administering a 5-HTR 1B inhibitor to the subject, wherein the administration of the 5-HTR 1B inhibitor to the subject induces cell death in the AML cells; and,   (b) continuing administration of the 5-HTR 1B inhibitor to the subject if the treatment with 5-HTR 1B inhibitor is being effective, or   (c) discontinuing administration of the 5-HTR 1B inhibitor to the subject if the treatment with 5-HTR 1B inhibitor is being ineffective,   wherein   (i) a decreased 5-HTR 1B expression level after the treatment with 5-HTR 1B inhibitor with respect to the 5-HTR 1B expression level prior to the treatment with 5-HTR 1B inhibitor indicates that the treatment with 5-HTR 1B inhibitor is effective; and,   (ii) an increased 5-HTR 1B expression level the treatment with 5-HTR 1B inhibitor with respect to the 5-HTR 1B expression level prior to the treatment with 5-HTR 1B inhibitor indicates that the treatment with 5-HTR 1B inhibitor is ineffective.   
     
     
         44 . The method of  claim 43 , wherein the 5-HTR 1B inhibitor is selected from the group consisting of methiothepin, alprenolol, AR-A000002, asenapine, cynipindolol, GR-127,935, iodocyanopindolol, isamoltane, metergoline, oxprenolol, pindolol, propranolol, SN-216,641, yohimbine, GR-55562, SB-224289, SB-236057, and a pharmaceutically acceptable salt thereof. 
     
     
         45 . The method of  claim 43 , wherein the expression of 5-HTR 1B in AML cells is detected by measuring the level of 5-HTR 1B proteins. 
     
     
         46 . The method of  claim 45 , wherein the expression of 5-HTR 1B in AML cells is detected by measuring the level of mRNA encoded by 5-HTR 1B genes. 
     
     
         47 . The method of  claim 45 , wherein the expression level of 5-HTR 1B proteins is determined by Western blot or immunocytochemistry. 
     
     
         48 . The method of  claim 46 , wherein the expression level of 5-HTR 1B genes is determined by PCR. 
     
     
         49 . The method of  claim 43 , wherein the expression of 5-HTR 1B is determined in a blood sample. 
     
     
         50 . The method of  claim 49 , wherein the blood sample is a peripheral blood sample.