The forkhead box C1 (FOXC1) transcription factor is downregulated in acute promyelocytic leukemia

Emiliano Fabiani, Giulia Falconi, Nélida Inés Noguera, Ernestina Saulle, Laura Cicconi, Mariadomenica Divona, Cristina Banella, Alessandra Picardi, Anna Maria Cerio, Letizia Boe, Massimo Sanchez, Elvira Pelosi, Ugo Testa, Francesco Lo-Coco, Maria Teresa Voso

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Forkhead box (FOX) genes encode transcription factors, which regulate embryogenesis and play an important role in hematopoietic differentiation and in mesenchymal niche maintenance. Overexpression of the family member FOXC1 has been reported in solid tumors and acute myeloid leukemia (AML). We studied FOXC1 expression and function in acute promyelocytic leukemia (APL) and normal hematopoietic progenitors. FOXC1 mRNA and protein levels were significantly lower in primary marrow samples from 27 APL patients, as compared to samples obtained from 27 patients with other AML subtypes, and 5 normal CD34+ hematopoietic cells. FOXC1 expression significantly increased in APL samples at the time of remission following consolidation treatment. In cell lines overexpressing PML-RARA, and in the NB4 t(15;17)-positive cell line, FOXC1 expression was lower than in other non-APL cell lines, and increased following treatment with all-trans retinoic acid (ATRA), due to functional binding of ATRA to the FOXC1 promoter region. Reduced FOXC1 expression was also associated to DNA hypermethylation of the +354 to +568 FOXC1 region, both in primary APL, and in NB4 cells. Treatment of NB4 cells with decitabine demethylated FOXC1 and upregulated its expression. Our findings indicate that FOXC1 is consistently repressed in APL due to hypermethylation and the presence of the PML-RARA rearrangement. A potential role of hypomethylating treatment in advanced APL remains to be established.

Original languageEnglish
Pages (from-to)84074-84085
Number of pages12
JournalOncotarget
Volume8
Issue number48
DOIs
Publication statusPublished - Oct 13 2017

Fingerprint

Forkhead Transcription Factors
Acute Promyelocytic Leukemia
Down-Regulation
decitabine
Tretinoin
Acute Myeloid Leukemia
Cell Line
Therapeutics
Genetic Promoter Regions
Embryonic Development
Leukemia
Transcription Factors
Bone Marrow
Maintenance
Messenger RNA
DNA
Genes
Neoplasms

Cite this

Fabiani, E., Falconi, G., Noguera, N. I., Saulle, E., Cicconi, L., Divona, M., ... Voso, M. T. (2017). The forkhead box C1 (FOXC1) transcription factor is downregulated in acute promyelocytic leukemia. Oncotarget, 8(48), 84074-84085. https://doi.org/10.18632/oncotarget.21101

The forkhead box C1 (FOXC1) transcription factor is downregulated in acute promyelocytic leukemia. / Fabiani, Emiliano; Falconi, Giulia; Noguera, Nélida Inés; Saulle, Ernestina; Cicconi, Laura; Divona, Mariadomenica; Banella, Cristina; Picardi, Alessandra; Cerio, Anna Maria; Boe, Letizia; Sanchez, Massimo; Pelosi, Elvira; Testa, Ugo; Lo-Coco, Francesco; Voso, Maria Teresa.

In: Oncotarget, Vol. 8, No. 48, 13.10.2017, p. 84074-84085.

Research output: Contribution to journalArticle

Fabiani, E, Falconi, G, Noguera, NI, Saulle, E, Cicconi, L, Divona, M, Banella, C, Picardi, A, Cerio, AM, Boe, L, Sanchez, M, Pelosi, E, Testa, U, Lo-Coco, F & Voso, MT 2017, 'The forkhead box C1 (FOXC1) transcription factor is downregulated in acute promyelocytic leukemia', Oncotarget, vol. 8, no. 48, pp. 84074-84085. https://doi.org/10.18632/oncotarget.21101
Fabiani, Emiliano ; Falconi, Giulia ; Noguera, Nélida Inés ; Saulle, Ernestina ; Cicconi, Laura ; Divona, Mariadomenica ; Banella, Cristina ; Picardi, Alessandra ; Cerio, Anna Maria ; Boe, Letizia ; Sanchez, Massimo ; Pelosi, Elvira ; Testa, Ugo ; Lo-Coco, Francesco ; Voso, Maria Teresa. / The forkhead box C1 (FOXC1) transcription factor is downregulated in acute promyelocytic leukemia. In: Oncotarget. 2017 ; Vol. 8, No. 48. pp. 84074-84085.
@article{11718677f4b14d67b7e59e2715fd7269,
title = "The forkhead box C1 (FOXC1) transcription factor is downregulated in acute promyelocytic leukemia",
abstract = "Forkhead box (FOX) genes encode transcription factors, which regulate embryogenesis and play an important role in hematopoietic differentiation and in mesenchymal niche maintenance. Overexpression of the family member FOXC1 has been reported in solid tumors and acute myeloid leukemia (AML). We studied FOXC1 expression and function in acute promyelocytic leukemia (APL) and normal hematopoietic progenitors. FOXC1 mRNA and protein levels were significantly lower in primary marrow samples from 27 APL patients, as compared to samples obtained from 27 patients with other AML subtypes, and 5 normal CD34+ hematopoietic cells. FOXC1 expression significantly increased in APL samples at the time of remission following consolidation treatment. In cell lines overexpressing PML-RARA, and in the NB4 t(15;17)-positive cell line, FOXC1 expression was lower than in other non-APL cell lines, and increased following treatment with all-trans retinoic acid (ATRA), due to functional binding of ATRA to the FOXC1 promoter region. Reduced FOXC1 expression was also associated to DNA hypermethylation of the +354 to +568 FOXC1 region, both in primary APL, and in NB4 cells. Treatment of NB4 cells with decitabine demethylated FOXC1 and upregulated its expression. Our findings indicate that FOXC1 is consistently repressed in APL due to hypermethylation and the presence of the PML-RARA rearrangement. A potential role of hypomethylating treatment in advanced APL remains to be established.",
author = "Emiliano Fabiani and Giulia Falconi and Noguera, {N{\'e}lida In{\'e}s} and Ernestina Saulle and Laura Cicconi and Mariadomenica Divona and Cristina Banella and Alessandra Picardi and Cerio, {Anna Maria} and Letizia Boe and Massimo Sanchez and Elvira Pelosi and Ugo Testa and Francesco Lo-Coco and Voso, {Maria Teresa}",
year = "2017",
month = "10",
day = "13",
doi = "10.18632/oncotarget.21101",
language = "English",
volume = "8",
pages = "84074--84085",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "48",

}

TY - JOUR

T1 - The forkhead box C1 (FOXC1) transcription factor is downregulated in acute promyelocytic leukemia

AU - Fabiani, Emiliano

AU - Falconi, Giulia

AU - Noguera, Nélida Inés

AU - Saulle, Ernestina

AU - Cicconi, Laura

AU - Divona, Mariadomenica

AU - Banella, Cristina

AU - Picardi, Alessandra

AU - Cerio, Anna Maria

AU - Boe, Letizia

AU - Sanchez, Massimo

AU - Pelosi, Elvira

AU - Testa, Ugo

AU - Lo-Coco, Francesco

AU - Voso, Maria Teresa

PY - 2017/10/13

Y1 - 2017/10/13

N2 - Forkhead box (FOX) genes encode transcription factors, which regulate embryogenesis and play an important role in hematopoietic differentiation and in mesenchymal niche maintenance. Overexpression of the family member FOXC1 has been reported in solid tumors and acute myeloid leukemia (AML). We studied FOXC1 expression and function in acute promyelocytic leukemia (APL) and normal hematopoietic progenitors. FOXC1 mRNA and protein levels were significantly lower in primary marrow samples from 27 APL patients, as compared to samples obtained from 27 patients with other AML subtypes, and 5 normal CD34+ hematopoietic cells. FOXC1 expression significantly increased in APL samples at the time of remission following consolidation treatment. In cell lines overexpressing PML-RARA, and in the NB4 t(15;17)-positive cell line, FOXC1 expression was lower than in other non-APL cell lines, and increased following treatment with all-trans retinoic acid (ATRA), due to functional binding of ATRA to the FOXC1 promoter region. Reduced FOXC1 expression was also associated to DNA hypermethylation of the +354 to +568 FOXC1 region, both in primary APL, and in NB4 cells. Treatment of NB4 cells with decitabine demethylated FOXC1 and upregulated its expression. Our findings indicate that FOXC1 is consistently repressed in APL due to hypermethylation and the presence of the PML-RARA rearrangement. A potential role of hypomethylating treatment in advanced APL remains to be established.

AB - Forkhead box (FOX) genes encode transcription factors, which regulate embryogenesis and play an important role in hematopoietic differentiation and in mesenchymal niche maintenance. Overexpression of the family member FOXC1 has been reported in solid tumors and acute myeloid leukemia (AML). We studied FOXC1 expression and function in acute promyelocytic leukemia (APL) and normal hematopoietic progenitors. FOXC1 mRNA and protein levels were significantly lower in primary marrow samples from 27 APL patients, as compared to samples obtained from 27 patients with other AML subtypes, and 5 normal CD34+ hematopoietic cells. FOXC1 expression significantly increased in APL samples at the time of remission following consolidation treatment. In cell lines overexpressing PML-RARA, and in the NB4 t(15;17)-positive cell line, FOXC1 expression was lower than in other non-APL cell lines, and increased following treatment with all-trans retinoic acid (ATRA), due to functional binding of ATRA to the FOXC1 promoter region. Reduced FOXC1 expression was also associated to DNA hypermethylation of the +354 to +568 FOXC1 region, both in primary APL, and in NB4 cells. Treatment of NB4 cells with decitabine demethylated FOXC1 and upregulated its expression. Our findings indicate that FOXC1 is consistently repressed in APL due to hypermethylation and the presence of the PML-RARA rearrangement. A potential role of hypomethylating treatment in advanced APL remains to be established.

U2 - 10.18632/oncotarget.21101

DO - 10.18632/oncotarget.21101

M3 - Article

VL - 8

SP - 84074

EP - 84085

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 48

ER -