Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides - Cutaneous T-cell lymphoma: Clinical implications

M. Alcántara-Hernández, C. Torres-Zárate, G. Pérez-Montesinos, F. Jurado-Santacruz, M. A. Domínguez-Gõmez, A. Peniche-Castellanos, E. Ferat-Osorio, N. Neri, M. J. Nambo, I. Alvarado-Cabrero, M. Moreno-Lafont, S. Huerta-Yepez, L. C. Bonifaz

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4 + T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4 + T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4 + T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4 + T cells. In addition, we found a decrease in the percentage of FoxP3 + cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3 + T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome. What's new? The most common variant of cutaneous T-cell lymphoma is mycosis fungoides (MF). In MF, expression of the FoxP3 transcription factor decreases. This paper looked at the relationship between FoxP3 and another transcription factor, HIF-1 α, and their influence on MF. In skin lesions from patients with the disease, the authors found excess HIF-1 α compared with controls. They also observed that HIF-1 α levels rise, and FoxP3 levels fall, as the disease progresses. When they blocked HIF-1 α, more FoxP3+ cells arose, suggesting that overexpression of HIF-1 α does reduce FoxP3 levels and perhaps promote disease progression. © 2013 UICC.
Original languageAmerican English
Pages (from-to)2136-2145
Number of pages1921
JournalInternational Journal of Cancer
DOIs
StatePublished - 1 May 2014

Fingerprint

Hypoxia-Inducible Factor 1
Cutaneous T-Cell Lymphoma
Mycosis Fungoides
Skin
T-Lymphocytes
Disease Progression
Forkhead Transcription Factors

Cite this

Alcántara-Hernández, M., Torres-Zárate, C., Pérez-Montesinos, G., Jurado-Santacruz, F., Domínguez-Gõmez, M. A., Peniche-Castellanos, A., ... Bonifaz, L. C. (2014). Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides - Cutaneous T-cell lymphoma: Clinical implications. International Journal of Cancer, 2136-2145. https://doi.org/10.1002/ijc.28546
Alcántara-Hernández, M. ; Torres-Zárate, C. ; Pérez-Montesinos, G. ; Jurado-Santacruz, F. ; Domínguez-Gõmez, M. A. ; Peniche-Castellanos, A. ; Ferat-Osorio, E. ; Neri, N. ; Nambo, M. J. ; Alvarado-Cabrero, I. ; Moreno-Lafont, M. ; Huerta-Yepez, S. ; Bonifaz, L. C. / Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides - Cutaneous T-cell lymphoma: Clinical implications. In: International Journal of Cancer. 2014 ; pp. 2136-2145.
@article{b14f988e1d594b7aa440b86bcf9e2e5e,
title = "Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides - Cutaneous T-cell lymphoma: Clinical implications",
abstract = "Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4 + T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4 + T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4 + T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4 + T cells. In addition, we found a decrease in the percentage of FoxP3 + cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3 + T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome. What's new? The most common variant of cutaneous T-cell lymphoma is mycosis fungoides (MF). In MF, expression of the FoxP3 transcription factor decreases. This paper looked at the relationship between FoxP3 and another transcription factor, HIF-1 α, and their influence on MF. In skin lesions from patients with the disease, the authors found excess HIF-1 α compared with controls. They also observed that HIF-1 α levels rise, and FoxP3 levels fall, as the disease progresses. When they blocked HIF-1 α, more FoxP3+ cells arose, suggesting that overexpression of HIF-1 α does reduce FoxP3 levels and perhaps promote disease progression. {\circledC} 2013 UICC.",
author = "M. Alc{\'a}ntara-Hern{\'a}ndez and C. Torres-Z{\'a}rate and G. P{\'e}rez-Montesinos and F. Jurado-Santacruz and Dom{\'i}nguez-G{\~o}mez, {M. A.} and A. Peniche-Castellanos and E. Ferat-Osorio and N. Neri and Nambo, {M. J.} and I. Alvarado-Cabrero and M. Moreno-Lafont and S. Huerta-Yepez and Bonifaz, {L. C.}",
year = "2014",
month = "5",
day = "1",
doi = "10.1002/ijc.28546",
language = "American English",
pages = "2136--2145",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",

}

Alcántara-Hernández, M, Torres-Zárate, C, Pérez-Montesinos, G, Jurado-Santacruz, F, Domínguez-Gõmez, MA, Peniche-Castellanos, A, Ferat-Osorio, E, Neri, N, Nambo, MJ, Alvarado-Cabrero, I, Moreno-Lafont, M, Huerta-Yepez, S & Bonifaz, LC 2014, 'Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides - Cutaneous T-cell lymphoma: Clinical implications', International Journal of Cancer, pp. 2136-2145. https://doi.org/10.1002/ijc.28546

Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides - Cutaneous T-cell lymphoma: Clinical implications. / Alcántara-Hernández, M.; Torres-Zárate, C.; Pérez-Montesinos, G.; Jurado-Santacruz, F.; Domínguez-Gõmez, M. A.; Peniche-Castellanos, A.; Ferat-Osorio, E.; Neri, N.; Nambo, M. J.; Alvarado-Cabrero, I.; Moreno-Lafont, M.; Huerta-Yepez, S.; Bonifaz, L. C.

In: International Journal of Cancer, 01.05.2014, p. 2136-2145.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides - Cutaneous T-cell lymphoma: Clinical implications

AU - Alcántara-Hernández, M.

AU - Torres-Zárate, C.

AU - Pérez-Montesinos, G.

AU - Jurado-Santacruz, F.

AU - Domínguez-Gõmez, M. A.

AU - Peniche-Castellanos, A.

AU - Ferat-Osorio, E.

AU - Neri, N.

AU - Nambo, M. J.

AU - Alvarado-Cabrero, I.

AU - Moreno-Lafont, M.

AU - Huerta-Yepez, S.

AU - Bonifaz, L. C.

PY - 2014/5/1

Y1 - 2014/5/1

N2 - Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4 + T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4 + T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4 + T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4 + T cells. In addition, we found a decrease in the percentage of FoxP3 + cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3 + T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome. What's new? The most common variant of cutaneous T-cell lymphoma is mycosis fungoides (MF). In MF, expression of the FoxP3 transcription factor decreases. This paper looked at the relationship between FoxP3 and another transcription factor, HIF-1 α, and their influence on MF. In skin lesions from patients with the disease, the authors found excess HIF-1 α compared with controls. They also observed that HIF-1 α levels rise, and FoxP3 levels fall, as the disease progresses. When they blocked HIF-1 α, more FoxP3+ cells arose, suggesting that overexpression of HIF-1 α does reduce FoxP3 levels and perhaps promote disease progression. © 2013 UICC.

AB - Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4 + T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4 + T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4 + T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4 + T cells. In addition, we found a decrease in the percentage of FoxP3 + cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3 + T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome. What's new? The most common variant of cutaneous T-cell lymphoma is mycosis fungoides (MF). In MF, expression of the FoxP3 transcription factor decreases. This paper looked at the relationship between FoxP3 and another transcription factor, HIF-1 α, and their influence on MF. In skin lesions from patients with the disease, the authors found excess HIF-1 α compared with controls. They also observed that HIF-1 α levels rise, and FoxP3 levels fall, as the disease progresses. When they blocked HIF-1 α, more FoxP3+ cells arose, suggesting that overexpression of HIF-1 α does reduce FoxP3 levels and perhaps promote disease progression. © 2013 UICC.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84896732610&origin=inward

UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84896732610&origin=inward

U2 - 10.1002/ijc.28546

DO - 10.1002/ijc.28546

M3 - Article

SP - 2136

EP - 2145

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

ER -

Alcántara-Hernández M, Torres-Zárate C, Pérez-Montesinos G, Jurado-Santacruz F, Domínguez-Gõmez MA, Peniche-Castellanos A et al. Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides - Cutaneous T-cell lymphoma: Clinical implications. International Journal of Cancer. 2014 May 1;2136-2145. https://doi.org/10.1002/ijc.28546