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

a hematopoietic tumor and diagnostic marker technology, applied in the direction of heterocyclic compound active ingredients, instruments, drug compositions, etc., can solve the problems of difficult to distinguish bpdcn from other hematopoietic neoplasms in practice, difficult to distinguish bpdcn from aml skin infiltration, and leukemic chang

Pending Publication Date: 2019-01-17
JAPANESE FOUND FOR CANCER RES
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Benefits of technology

The present invention has led to a new therapeutic drug for BPDCN by identifying specific markers to treat the condition. It can also be used for screening new therapeutic drugs.

Problems solved by technology

BPDCN often responds to chemotherapy at the beginning but recurs early, resulting in leukemic change.
Along with the rarity of the disease, BPDCN is difficult to be distinguished from other hematopoietic neoplasms in practice.
Particularly, distinguishing BPDCN from the skin infiltration of AML is most difficult because of its cytomorphology, immunophenotype, and clinical conditions (Non Patent Literatures 2 to 4).

Method used

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

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Embodiment Construction

[0046]The present inventors have conducted detailed molecular pathological studies on BPDCN and consequently found markers that can divide BPDCN into at least two subtypes. The present inventors have revealed that neoplasms currently diagnosed as BPDCN can be divided into two subtypes on the basis of 8q24 rearrangement, MYC expression, and cytomorphology, though the details will be described below.

[0047]8q24 rearrangement, one of the markers for subtyping of BPDCN, may be detected by use of any method such as G-banding or split FISH as long as the method can detect the rearrangement of the region.

[0048]Increased expression of MYC may be detected by use of any method as long as the method is capable of detecting the MYC expression at the protein level or the RNA level. The method for analysis at the protein level includes immunostaining, Western blot, and the like. The method for analysis at the RNA level includes RT-PCR, quantitative RT-PCR, cDNA microarray method, RNA sequencing us...

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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.

Description

TECHNICAL FIELD[0001]The present invention relates to diagnostic markers of blastic plasmacytoid dendritic cell neoplasm (BPDCN) which is a rare hematopoietic neoplasm, and a method for screening for a novel therapeutic drug.BACKGROUND ART[0002]Blastic plasmacytoid dendritic cell neoplasm (hereinafter, referred to as BPDCN) is a rare hematopoietic neoplasm reportedly derived from undifferentiated plasmacytoid dendritic cells (pDC). Typically, this neoplasm develops skin lesions and is an aggressive disease with poor prognosis and a median survival period about of 12 months. BPDCN often responds to chemotherapy at the beginning but recurs early, resulting in leukemic change.[0003]BPDCN was reported as skin lymphoma positive for CD4 and CD56 and negative for T cell markers in 1994 by Adachi et al. (Non Patent Literature 1). Since then, also because of being a rare disease, its name had been changed many times due to change in disease concepts until the name of BPDCN appeared as an ind...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886A61K31/167A61K31/4045A61K31/635G01N33/50A61K31/55A61K31/675
CPCC12Q1/6886A61K31/167A61K31/4045A61K31/635G01N2333/82A61K31/55A61K31/675C12Q2600/158C12Q2600/16G01N33/5023A61K45/00A61K31/4745A61K31/551G01N33/5011G01N33/5047G01N33/57426G01N33/5748G01N2800/56A61P35/02A61P43/00G01N33/48C12Q1/68
Inventor TAKEUCHI, KENGOSAKAMOTO, KANAKATAYAMA, RYOHEISAKATA, SEIJI
Owner JAPANESE FOUND FOR CANCER RES
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