The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis

Monica Cardone; Ayten Kandilci; Cintia Carella; Jonas A Nilsson; Jennifer A Brennan; Sema Sirma; Ugur Ozbek; Kelli Boyd; John L Cleveland; Gerard C Grosveld

doi:10.1128/MCB.25.6.2395-2405.2005

The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis

Monica Cardone, Ayten Kandilci, Cintia Carella, Jonas A Nilsson, Jennifer A Brennan, Sema Sirma, Ugur Ozbek, Kelli Boyd, John L Cleveland, Gerard C Grosveld

UWA Centre for Medical Research (affiliated with the Harry Perkins Institute of Medical Research)

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

Abstract

The human ETS family gene TEL2/ETV7 is highly homologous to TEL1/ETV6, a frequent target of chromosome translocations in human leukemia and specific solid tumors. Here we report that TEL2 augments the proliferation and survival of normal mouse B cells and dramatically accelerates lymphoma development in Emu-Myc transgenic mice. Nonetheless, inactivation of the p53 pathway was a hallmark of all TEL2/Emu-Myc lymphomas, indicating that TEL2 expression alone is insufficient to bypass this apoptotic checkpoint. Although TEL2 is infrequently up-regulated in human sporadic Burkitt's lymphoma, analysis of pediatric B-cell acute lymphocytic leukemia (B-ALL) samples showed increased coexpression of TEL2 and MYC and/or MYCN in over one-third of B-ALL patients. Therefore, TEL2 and MYC also appear to cooperate in provoking a cadre of human B-cell malignancies.

Original language	English
Pages (from-to)	2395-405
Number of pages	11
Journal	Molecular and Cellular Biology
Volume	25
Issue number	6
DOIs	https://doi.org/10.1128/MCB.25.6.2395-2405.2005
Publication status	Published - Mar 2005

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@article{36397ae4ef5642bcb50a8820054441c3,

title = "The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis",

abstract = "The human ETS family gene TEL2/ETV7 is highly homologous to TEL1/ETV6, a frequent target of chromosome translocations in human leukemia and specific solid tumors. Here we report that TEL2 augments the proliferation and survival of normal mouse B cells and dramatically accelerates lymphoma development in Emu-Myc transgenic mice. Nonetheless, inactivation of the p53 pathway was a hallmark of all TEL2/Emu-Myc lymphomas, indicating that TEL2 expression alone is insufficient to bypass this apoptotic checkpoint. Although TEL2 is infrequently up-regulated in human sporadic Burkitt's lymphoma, analysis of pediatric B-cell acute lymphocytic leukemia (B-ALL) samples showed increased coexpression of TEL2 and MYC and/or MYCN in over one-third of B-ALL patients. Therefore, TEL2 and MYC also appear to cooperate in provoking a cadre of human B-cell malignancies.",

keywords = "Animals, Apoptosis, B-Lymphocytes/metabolism, Burkitt Lymphoma/genetics, Cell Proliferation, Child, DNA-Binding Proteins/genetics, Female, Humans, Male, Mice, Mice, Transgenic, Mutation/genetics, Proto-Oncogene Proteins c-ets, Proto-Oncogene Proteins c-myc/metabolism, Suppression, Genetic, Transcription Factors/genetics, Tumor Suppressor Protein p53/genetics, Up-Regulation/genetics",

author = "Monica Cardone and Ayten Kandilci and Cintia Carella and Nilsson, {Jonas A} and Brennan, {Jennifer A} and Sema Sirma and Ugur Ozbek and Kelli Boyd and Cleveland, {John L} and Grosveld, {Gerard C}",

year = "2005",

month = mar,

doi = "10.1128/MCB.25.6.2395-2405.2005",

language = "English",

volume = "25",

pages = "2395--405",

journal = "Molecular and Cellular Biology",

issn = "0270-7306",

publisher = "American Society for Microbiology",

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TY - JOUR

T1 - The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis

AU - Cardone, Monica

AU - Kandilci, Ayten

AU - Carella, Cintia

AU - Nilsson, Jonas A

AU - Brennan, Jennifer A

AU - Sirma, Sema

AU - Ozbek, Ugur

AU - Boyd, Kelli

AU - Cleveland, John L

AU - Grosveld, Gerard C

PY - 2005/3

Y1 - 2005/3

N2 - The human ETS family gene TEL2/ETV7 is highly homologous to TEL1/ETV6, a frequent target of chromosome translocations in human leukemia and specific solid tumors. Here we report that TEL2 augments the proliferation and survival of normal mouse B cells and dramatically accelerates lymphoma development in Emu-Myc transgenic mice. Nonetheless, inactivation of the p53 pathway was a hallmark of all TEL2/Emu-Myc lymphomas, indicating that TEL2 expression alone is insufficient to bypass this apoptotic checkpoint. Although TEL2 is infrequently up-regulated in human sporadic Burkitt's lymphoma, analysis of pediatric B-cell acute lymphocytic leukemia (B-ALL) samples showed increased coexpression of TEL2 and MYC and/or MYCN in over one-third of B-ALL patients. Therefore, TEL2 and MYC also appear to cooperate in provoking a cadre of human B-cell malignancies.

AB - The human ETS family gene TEL2/ETV7 is highly homologous to TEL1/ETV6, a frequent target of chromosome translocations in human leukemia and specific solid tumors. Here we report that TEL2 augments the proliferation and survival of normal mouse B cells and dramatically accelerates lymphoma development in Emu-Myc transgenic mice. Nonetheless, inactivation of the p53 pathway was a hallmark of all TEL2/Emu-Myc lymphomas, indicating that TEL2 expression alone is insufficient to bypass this apoptotic checkpoint. Although TEL2 is infrequently up-regulated in human sporadic Burkitt's lymphoma, analysis of pediatric B-cell acute lymphocytic leukemia (B-ALL) samples showed increased coexpression of TEL2 and MYC and/or MYCN in over one-third of B-ALL patients. Therefore, TEL2 and MYC also appear to cooperate in provoking a cadre of human B-cell malignancies.

KW - Animals

KW - Apoptosis

KW - B-Lymphocytes/metabolism

KW - Burkitt Lymphoma/genetics

KW - Cell Proliferation

KW - Child

KW - DNA-Binding Proteins/genetics

KW - Female

KW - Humans

KW - Male

KW - Mice

KW - Mice, Transgenic

KW - Mutation/genetics

KW - Proto-Oncogene Proteins c-ets

KW - Proto-Oncogene Proteins c-myc/metabolism

KW - Suppression, Genetic

KW - Transcription Factors/genetics

KW - Tumor Suppressor Protein p53/genetics

KW - Up-Regulation/genetics

U2 - 10.1128/MCB.25.6.2395-2405.2005

DO - 10.1128/MCB.25.6.2395-2405.2005

M3 - Article

C2 - 15743832

SN - 0270-7306

VL - 25

SP - 2395

EP - 2405

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 6

ER -

The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis

Abstract

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