PLM/RARα, a Fusion Protein in Acute Promyelocytic Leukemia, Prevents Growth Factor Withdrawal-Induced Apoptosis in TF-1 Cells

Siqing Fu, Ugo Consoli, Elie G. Hanania, Zhifei Zu, David Claxton, Michael Andreeff, Albert B. Deisseroth

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A unique mRNA produced by the t(15;17)(q22-24;q11-21) translocation in the leukemic cells of acute promyelocytic leukemia patients encodes a chimeric protein, PML/ RARα, which is formed by the fusion of the retinoic acid receptor a (RARα) and the promyelocytic locus gene (PML). This translocation is often the only visible karyotypic aberration present which is detected in almost 100% of acute promyelocytic leukemia patients. As an initial step to study the role of PML/RARα in leukemogenesis, we attempted to express the fusion protein in hematopoietic cells through retrovirus-mediated gene transfer of the retroviral vector, pGPRCHT, which contains the PML/RARα cDNA. Transduction of the PML/RARα cDNA fragment used in this vector, which extends from the position 31 bp to the position 2638 bp in a transcription unit driven by the Moloney murine sarcoma virus LTR, was found to abrogate the growth factor dependence of TF-1 cells. In addition, introduction of PML/RARα into TF-1 cells can protect these cells from the apoptosis usually induced in TF-1 cells by growth factor withdrawal, as measured by three assays for apoptosis: morphology, DNA ladder formation, and end labeling of nicked DNA with fluorescent-conjugated nucleotide precursors followed by a fluorescence-activated cell sorting assay. These data suggest that the PML/RARα fusion protein may inhibit programmed cell death in myeloid cells.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalClinical Cancer Research
Volume1
Issue number6
StatePublished - Jun 1 1995

Fingerprint

Acute Promyelocytic Leukemia
Retinoic Acid Receptors
Intercellular Signaling Peptides and Proteins
Apoptosis
Genes
Proteins
Complementary DNA
Moloney murine sarcoma virus
DNA
Myeloid Cells
Retroviridae
Flow Cytometry
Cell Death
Nucleotides
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Fu, Siqing ; Consoli, Ugo ; Hanania, Elie G. ; Zu, Zhifei ; Claxton, David ; Andreeff, Michael ; Deisseroth, Albert B. / PLM/RARα, a Fusion Protein in Acute Promyelocytic Leukemia, Prevents Growth Factor Withdrawal-Induced Apoptosis in TF-1 Cells. In: Clinical Cancer Research. 1995 ; Vol. 1, No. 6. pp. 583-590.
@article{5cc1896e73e6424db1e796f548c6cf75,
title = "PLM/RARα, a Fusion Protein in Acute Promyelocytic Leukemia, Prevents Growth Factor Withdrawal-Induced Apoptosis in TF-1 Cells",
abstract = "A unique mRNA produced by the t(15;17)(q22-24;q11-21) translocation in the leukemic cells of acute promyelocytic leukemia patients encodes a chimeric protein, PML/ RARα, which is formed by the fusion of the retinoic acid receptor a (RARα) and the promyelocytic locus gene (PML). This translocation is often the only visible karyotypic aberration present which is detected in almost 100{\%} of acute promyelocytic leukemia patients. As an initial step to study the role of PML/RARα in leukemogenesis, we attempted to express the fusion protein in hematopoietic cells through retrovirus-mediated gene transfer of the retroviral vector, pGPRCHT, which contains the PML/RARα cDNA. Transduction of the PML/RARα cDNA fragment used in this vector, which extends from the position 31 bp to the position 2638 bp in a transcription unit driven by the Moloney murine sarcoma virus LTR, was found to abrogate the growth factor dependence of TF-1 cells. In addition, introduction of PML/RARα into TF-1 cells can protect these cells from the apoptosis usually induced in TF-1 cells by growth factor withdrawal, as measured by three assays for apoptosis: morphology, DNA ladder formation, and end labeling of nicked DNA with fluorescent-conjugated nucleotide precursors followed by a fluorescence-activated cell sorting assay. These data suggest that the PML/RARα fusion protein may inhibit programmed cell death in myeloid cells.",
author = "Siqing Fu and Ugo Consoli and Hanania, {Elie G.} and Zhifei Zu and David Claxton and Michael Andreeff and Deisseroth, {Albert B.}",
year = "1995",
month = "6",
day = "1",
language = "English (US)",
volume = "1",
pages = "583--590",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

PLM/RARα, a Fusion Protein in Acute Promyelocytic Leukemia, Prevents Growth Factor Withdrawal-Induced Apoptosis in TF-1 Cells. / Fu, Siqing; Consoli, Ugo; Hanania, Elie G.; Zu, Zhifei; Claxton, David; Andreeff, Michael; Deisseroth, Albert B.

In: Clinical Cancer Research, Vol. 1, No. 6, 01.06.1995, p. 583-590.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PLM/RARα, a Fusion Protein in Acute Promyelocytic Leukemia, Prevents Growth Factor Withdrawal-Induced Apoptosis in TF-1 Cells

AU - Fu, Siqing

AU - Consoli, Ugo

AU - Hanania, Elie G.

AU - Zu, Zhifei

AU - Claxton, David

AU - Andreeff, Michael

AU - Deisseroth, Albert B.

PY - 1995/6/1

Y1 - 1995/6/1

N2 - A unique mRNA produced by the t(15;17)(q22-24;q11-21) translocation in the leukemic cells of acute promyelocytic leukemia patients encodes a chimeric protein, PML/ RARα, which is formed by the fusion of the retinoic acid receptor a (RARα) and the promyelocytic locus gene (PML). This translocation is often the only visible karyotypic aberration present which is detected in almost 100% of acute promyelocytic leukemia patients. As an initial step to study the role of PML/RARα in leukemogenesis, we attempted to express the fusion protein in hematopoietic cells through retrovirus-mediated gene transfer of the retroviral vector, pGPRCHT, which contains the PML/RARα cDNA. Transduction of the PML/RARα cDNA fragment used in this vector, which extends from the position 31 bp to the position 2638 bp in a transcription unit driven by the Moloney murine sarcoma virus LTR, was found to abrogate the growth factor dependence of TF-1 cells. In addition, introduction of PML/RARα into TF-1 cells can protect these cells from the apoptosis usually induced in TF-1 cells by growth factor withdrawal, as measured by three assays for apoptosis: morphology, DNA ladder formation, and end labeling of nicked DNA with fluorescent-conjugated nucleotide precursors followed by a fluorescence-activated cell sorting assay. These data suggest that the PML/RARα fusion protein may inhibit programmed cell death in myeloid cells.

AB - A unique mRNA produced by the t(15;17)(q22-24;q11-21) translocation in the leukemic cells of acute promyelocytic leukemia patients encodes a chimeric protein, PML/ RARα, which is formed by the fusion of the retinoic acid receptor a (RARα) and the promyelocytic locus gene (PML). This translocation is often the only visible karyotypic aberration present which is detected in almost 100% of acute promyelocytic leukemia patients. As an initial step to study the role of PML/RARα in leukemogenesis, we attempted to express the fusion protein in hematopoietic cells through retrovirus-mediated gene transfer of the retroviral vector, pGPRCHT, which contains the PML/RARα cDNA. Transduction of the PML/RARα cDNA fragment used in this vector, which extends from the position 31 bp to the position 2638 bp in a transcription unit driven by the Moloney murine sarcoma virus LTR, was found to abrogate the growth factor dependence of TF-1 cells. In addition, introduction of PML/RARα into TF-1 cells can protect these cells from the apoptosis usually induced in TF-1 cells by growth factor withdrawal, as measured by three assays for apoptosis: morphology, DNA ladder formation, and end labeling of nicked DNA with fluorescent-conjugated nucleotide precursors followed by a fluorescence-activated cell sorting assay. These data suggest that the PML/RARα fusion protein may inhibit programmed cell death in myeloid cells.

UR - http://www.scopus.com/inward/record.url?scp=0028979233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028979233&partnerID=8YFLogxK

M3 - Article

VL - 1

SP - 583

EP - 590

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 6

ER -