Diagnosis marker for rare hematopoietic tumor, test method, therapeutic agent, and screening method

Abstract

The diagnostic markers that provide novel diagnostic criteria to blastic plasmacytoid dendritic cell neoplasm (BPDCN) has been searched, and the presence of immunoblastoid cytomorphology, 8q24 rearrangement, and MYC expression were established as novel markers for subtyping BPDCN. It has been further found that the inhibitors which directly or indirectly inhibit the expression, functions, or signaling pathways of MYC, such as BET bromodomain-selective inhibitors or aurora kinase inhibitors, are effective in MYC-positive BPDCN, and HDAC inhibitors or BCL2 family protein inhibitors are effective as therapeutic drugs for BPDCN.

1 - 12 . (canceled) 
     
     
         13 . Diagnostic markers to classify BPDCN, comprising
 an “immunoblastoid” morphological marker,   8q24 rearrangement, and/or   MYC expression   in BPDCN.   
     
     
         14 . A probe set for detecting the diagnostic marker according to  claim 13 , wherein
 the diagnostic marker is 8q24 rearrangement,   a telomeric probe which comprises a sequence of at least consecutive 20 bp in the sequence of CTD-2527N12 and is capable of specifically hybridizing to CTD-2527N12, and   a probe which comprises a sequence of at least consecutive 20 bp of a centromeric region positioned upstream of MYC gene and is capable of specifically hybridizing to the centromeric region.   
     
     
         15 . A test method to divide BPDCN into subtypes comprising,
 by testing at least any one of the diagnostic markers according to  claim 13 .   
     
     
         16 . A pharmaceutical composition for treating BPDCN comprising
 the active ingredient is at least one of BET (bromodomain and extra terminal) bromodomain-selective inhibitors, Aurora kinase inhibitors, HDAC inhibitors and BCL2 family protein inhibitors.   
     
     
         17 . The pharmaceutical composition according to  claim 16 ,
 the BPDCN to be treated is a subtype which is positive for at least any one marker selected from immunoblastoid cytomorphology, 8q24 rearrangement, and MYC expression,   an active ingredient for treatment is the BET bromodomain-selective inhibitor or the aurora kinase inhibitor.   
     
     
         18 . The pharmaceutical composition according to  claim 17 , wherein
 the BET bromodomain-selective inhibitor is JQ1, I-BET151, I-BET762, OTX015, CPI203, PFI-1 or an analog compound thereof, and   the aurora kinase inhibitor is alisertib, barasertib or an analog compound thereof.   
     
     
         19 . The pharmaceutical composition according to  claim 16 ,
 wherein the HDAC inhibitor is vorinostat, panobinostat or an analog compound thereof, and   the BCL2 family protein inhibitor is venetoclax or an analog compound thereof.   
     
     
         20 . A method for screening for a therapeutic drug for BPDCN, comprising
 adding a candidate compound to a medium of a BPDCN cell line, and   using change in MYC expression and/or cell growth by the candidate compound as an index.   
     
     
         21 . The method for screening for a therapeutic drug for BPDCN according to  claim 20 , wherein
 the BPDCN cell line is CAL-1 cell line and/or PMDC05 cell line.   
     
     
         22 . The method for screening for a therapeutic drug for BPDCN according to  claim 20 , comprising
 using change in MYC expression by a candidate compound as an index.