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Reducing irf4, dusp22, or flj43663 polypeptide expression

a polypeptide and expression technology, applied in the field of reducing irf4, dusp22, or flj43663 polypeptide expression, can solve the problem that ptcls are fatal in the majority of patients

Inactive Publication Date: 2010-12-23
MAYO FOUND FOR MEDICAL EDUCATION & RES
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009]In some cases, an agent that inhibits the expression of an DUSP22 polypeptide and / or an FLJ43663 polypeptide can be used to reduce the proliferation of abnormal T-lymphocytes (e.g., T-cell lymphomas). In addition, this document provides methods (e.g., in vivo and in vitro assays) for identifying agents (e.g., antibodies, siRNAs, or other compounds) that can reduce the expression of an DUSP22 polypeptide and / or an FLJ43663 polypeptide in a mammal.

Problems solved by technology

PTCLs are fatal in the majority of patients.

Method used

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  • Reducing irf4, dusp22, or flj43663 polypeptide expression
  • Reducing irf4, dusp22, or flj43663 polypeptide expression

Examples

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example 1

Recurrent Translocations Involving the IRF4 Oncogene in Peripheral T-Cell Lymphomas

[0070]Specimens from 169 patients with primary T-cell lymphomas (PTCL) diagnosed by WHO criteria were studied. There were 104 males and 65 females (M:F ratio, 1.6:1). The mean age was 58 years (range, 5-92 years). Cases included 23 angioimmunoblastic T-cell lymphomas (AITLs, 13%), 72 PTCL-unspecified (43%), 18 ALK-positive anaplastic large-cell lymphomas (ALCLs) (11%), 24 ALK-negative ALCLs (14%), 14 C-ALCLs (8%), and 18 other PTCLs (Table 1).

TABLE 1IRF4 Translocations and IRF4 Protein Expression in Peripheral T-cell LymphomasFISHImmunohistochemistryDiagnosis# pos.*%# pos.*%Angioimmunoblastic T-cell lymphoma0 / 190 0 / 23 0PTCL, unspecified3 / 64520 / 7228(CD30-positive)(1 / 17)(6)(13 / 18)(72)(CD30-negative)(2 / 47)(4) (7 / 54)(13)Anaplastic large cell lymphoma, ALK-positive0 / 18016 / 1794Anaplastic large cell lymphoma, ALK-negative1 / 23420 / 2291Cutaneous anaplastic large cell lymphoma8 / 1457 13 / 1493T-cell large granular ...

example 2

IRF4 Translocations are Specific for Cutaneous Anaplastic Large Cell Lymphoma

[0080]Skin biopsies involved by T-cell lymphoproliferative disorders from 68 patients were classified by WHO / EORTC criteria. Clinicopathologic data for classification included progression / regression of lesions, history of mycosis fungoides (MF) or other cutaneous T-cell lymphoproliferative disorders, anatomic site and timing of extracutaneous disease, morphology, immunophenotype, and T-cell clonality if needed. Cases that could not be classified definitively were excluded. FISH for IRF4 was performed using a breakapart probe. Positive cases also were screened for T-cell receptor (TCRA, TCRB, and TCRG) rearrangements. FISH was scored by a cytogeneticist using previously established normal ranges based on 95% confidence intervals.

[0081]Among cALCLs, 9 / 22 (41%) demonstrated abnormal separation of the IRF4 breakapart probe, indicating an IRF4 translocation. None of the 46 remaining T-cell lymphoproliferative di...

example 3

Human T-Cell Lymphoma Lines Express IRF4

[0083]To develop an in vitro model for studying IRF4 in T-cell lymphomas, human T-cell lymphoma cell lines were screened by western blot and immunohistochemistry. All T-cell lymphomas and, T-cell lymphoma cell lines tested (SUDHL-1, SR786, Karpas 299, SeAx, MyLa, and HuT78) were positive for IRF4. T-cell lymphoblastic leukemia cell lines were negative for IRF4 (FIG. 5A). Western blotting for MYC was also performed. Cell lines with weaker IRF4 expression also showed weaker expression of MYC (FIG. 5B).

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Abstract

This document relates to the activity of interferon regulatory factor 4 (IRF4) in T-cell lymphomas. For example, methods and materials involved in reducing the expression of an IRF4 polypeptide in T-cell lymphoma cells and identifying agents having the ability to reduce expression of an IRF4 polypeptide in T-cell lymphoma cells are provided. This document also relates to reducing DUSP22 or FLJ43663 polypeptide activity in T-cell lymphomas. For example, methods and materials involved in reducing the expression of DUSP22 polypeptides and / or FLJ43663 polypeptides in T-cell lymphoma cells and identifying agents having the ability to reduce expression of DUSP22 polypeptides and / or FLJ43663 polypeptides in T-cell lymphoma cells are provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is claims the benefit of U.S. Provisional Application Ser. No. 61 / 179,201, filed May 18, 2009. The disclosure of the prior application is considered part of (and is incorporated by reference in) the disclosure of this application.STATEMENT AS TO FEDERALLY SPONSORED RESEARCH[0002]Funding for the work described herein was provided by the federal government under grant number CA097274, awarded by the National Cancer Institute. The federal government has certain rights in the invention.BACKGROUND[0003]1. Technical Field[0004]This document relates to reducing interferon regulatory factor 4 (IRF4) activity in T-cell lymphomas. For example, methods and materials involved in reducing the expression of an IRF4 polypeptide in T-cell lymphoma cells and identifying agents having the ability to reduce expression of an IRF4 polypeptide in T-cell lymphoma cells are provided. This document also relates to reducing DUSP22 or FLJ43663 poly...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/713C12Q1/68G01N33/68A61P35/00
CPCA61K31/713G01N2333/4703G01N33/57407A61P35/00
Inventor FELDMAN, ANDREW L.DOGAN, AHMETVASMATZIS, GEORGELAW, MARKSMITH, DAVID I.
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
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