Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia

Diego A. Pereira-Martins; Juan L. Coelho-Silva; Isabel Weinhäuser; Pedro L. Franca-Neto; Douglas R. Silveira; César Ortiz; Amanda Moreira-Aguiar; Marinus M. Lima; Luisa C. Koury; Raul A. de Melo; Ana B. Glória; Evandro M Fagundes; Bruno K. Lino; Katia Pagnano; Rosane Bittencourt; Elenaide Nunes; Fabiola Traina; Lorena Figueiredo-Pontes; Armand Keating; Martin S. Tallman; Raul C. Ribeiro; Richard Dilon; Arnold Ganser; Miguel A. Sanz; Nancy Berliner; Peter Valk; Bob Löwenberg; Tiziana Ottone; Nelida I. Noguera; Maria T. Voso; Francesca Paoloni; Paola Fazi; Emanuele Ammatuna; Gerwin Huls; Jan Jacob Schuringa; Eduardo M. Rego; Antonio R. Lucena-Araujo

doi:10.1111/bjh.18510

Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia

Diego A. Pereira-Martins, Juan L. Coelho-Silva, Isabel Weinhäuser, Pedro L. Franca-Neto, Douglas R. Silveira, César Ortiz, Amanda Moreira-Aguiar, Marinus M. Lima, Luisa C. Koury, Raul A. de Melo, Ana B. Glória, Evandro M Fagundes, Bruno K. Lino, Katia Pagnano, Rosane Bittencourt, Elenaide Nunes, Fabiola Traina, Lorena Figueiredo-Pontes, Armand Keating, Martin S. TallmanRaul C. Ribeiro, Richard Dilon, Arnold Ganser, Miguel A. Sanz, Nancy Berliner, Peter Valk, Bob Löwenberg, Tiziana Ottone, Nelida I. Noguera, Maria T. Voso, Francesca Paoloni, Paola Fazi, Emanuele Ammatuna, Gerwin Huls, Jan Jacob Schuringa, Eduardo M. Rego, Antonio R. Lucena-Araujo^*

^*Corresponding author for this work

Hematology

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

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Abstract

Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA.

Original language	English
Pages (from-to)	170-174
Number of pages	5
Journal	British Journal of Haematology
Volume	200
Issue number	2
DOIs	https://doi.org/10.1111/bjh.18510
Publication status	E-pub ahead of print - 20 Oct 2022

Bibliographical note

Funding Information:
This investigation was supported by (CNPq; grant # 303479/2018‐3) and (FAPESP, Grant #2013/08135‐2). D.A.P.M. (Grant #2017/23117‐1), J.L.C.‐S. (Grant #2016/23191‐4) and I.W. (Grant #2015/09228‐0) received a fellowship from FAPESP. I.W and D.A.P‐M were sponsored by the Abel Tasman Talent Program of the Graduate School of Medical Sciences of the University of Groningen/University Medical Center Groningen, The Netherlands. Conselho Nacional de Desenvolvimento Científico e Tecnológico Fundação de Amparo à Pesquisa do Estado de São Paulo

Funding information
Conselho Nacional de Desenvolvimento
Científico e Tecnológico, Grant/Award
Number: 303479/2018-3; Fundação de
Amparo à Pesquisa do Estado de São Paulo,
Grant/Award Number: 2013/08135-2,
2015/09228-0, 2016/23191-4 and 2017/23117-1

Publisher Copyright:
© 2022 British Society for Haematology and John Wiley & Sons Ltd.

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Pereira-Martins, D. A., Coelho-Silva, J. L., Weinhäuser, I., Franca-Neto, P. L., Silveira, D. R., Ortiz, C., Moreira-Aguiar, A., Lima, M. M., Koury, L. C., de Melo, R. A., Glória, A. B., Fagundes, EM., Lino, B. K., Pagnano, K., Bittencourt, R., Nunes, E., Traina, F., Figueiredo-Pontes, L., Keating, A., ... Lucena-Araujo, A. R. (2022). Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia. British Journal of Haematology, 200(2), 170-174. https://doi.org/10.1111/bjh.18510

@article{0c0bdef69f6c4fbaba95d694023e4b02,

title = "Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia",

abstract = "Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA.",

author = "Pereira-Martins, {Diego A.} and Coelho-Silva, {Juan L.} and Isabel Weinh{\"a}user and Franca-Neto, {Pedro L.} and Silveira, {Douglas R.} and C{\'e}sar Ortiz and Amanda Moreira-Aguiar and Lima, {Marinus M.} and Koury, {Luisa C.} and {de Melo}, {Raul A.} and Gl{\'o}ria, {Ana B.} and Evandro M Fagundes and Lino, {Bruno K.} and Katia Pagnano and Rosane Bittencourt and Elenaide Nunes and Fabiola Traina and Lorena Figueiredo-Pontes and Armand Keating and Tallman, {Martin S.} and Ribeiro, {Raul C.} and Richard Dilon and Arnold Ganser and Sanz, {Miguel A.} and Nancy Berliner and Peter Valk and Bob L{\"o}wenberg and Tiziana Ottone and Noguera, {Nelida I.} and Voso, {Maria T.} and Francesca Paoloni and Paola Fazi and Emanuele Ammatuna and Gerwin Huls and Jan Jacob Schuringa and Rego, {Eduardo M.} and Lucena-Araujo, {Antonio R.}",

note = "Funding Information: This investigation was supported by (CNPq; grant # 303479/2018‐3) and (FAPESP, Grant #2013/08135‐2). D.A.P.M. (Grant #2017/23117‐1), J.L.C.‐S. (Grant #2016/23191‐4) and I.W. (Grant #2015/09228‐0) received a fellowship from FAPESP. I.W and D.A.P‐M were sponsored by the Abel Tasman Talent Program of the Graduate School of Medical Sciences of the University of Groningen/University Medical Center Groningen, The Netherlands. Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo Funding information Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico, Grant/Award Number: 303479/2018-3; Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo, Grant/Award Number: 2013/08135-2, 2015/09228-0, 2016/23191-4 and 2017/23117-1 Publisher Copyright: {\textcopyright} 2022 British Society for Haematology and John Wiley & Sons Ltd.",

year = "2022",

month = oct,

day = "20",

doi = "10.1111/bjh.18510",

language = "English",

volume = "200",

pages = "170--174",

journal = "British Journal of Haematology",

issn = "0007-1048",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "2",

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Pereira-Martins, DA, Coelho-Silva, JL, Weinhäuser, I, Franca-Neto, PL, Silveira, DR, Ortiz, C, Moreira-Aguiar, A, Lima, MM, Koury, LC, de Melo, RA, Glória, AB, Fagundes, EM, Lino, BK, Pagnano, K, Bittencourt, R, Nunes, E, Traina, F, Figueiredo-Pontes, L, Keating, A, Tallman, MS, Ribeiro, RC, Dilon, R, Ganser, A, Sanz, MA, Berliner, N, Valk, P , Löwenberg, B, Ottone, T, Noguera, NI, Voso, MT, Paoloni, F, Fazi, P, Ammatuna, E, Huls, G, Schuringa, JJ, Rego, EM & Lucena-Araujo, AR 2022, 'Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia', British Journal of Haematology, vol. 200, no. 2, pp. 170-174. https://doi.org/10.1111/bjh.18510

TY - JOUR

T1 - Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia

AU - Pereira-Martins, Diego A.

AU - Coelho-Silva, Juan L.

AU - Weinhäuser, Isabel

AU - Franca-Neto, Pedro L.

AU - Silveira, Douglas R.

AU - Ortiz, César

AU - Moreira-Aguiar, Amanda

AU - Lima, Marinus M.

AU - Koury, Luisa C.

AU - de Melo, Raul A.

AU - Glória, Ana B.

AU - Fagundes, Evandro M

AU - Lino, Bruno K.

AU - Pagnano, Katia

AU - Bittencourt, Rosane

AU - Nunes, Elenaide

AU - Traina, Fabiola

AU - Figueiredo-Pontes, Lorena

AU - Keating, Armand

AU - Tallman, Martin S.

AU - Ribeiro, Raul C.

AU - Dilon, Richard

AU - Ganser, Arnold

AU - Sanz, Miguel A.

AU - Berliner, Nancy

AU - Valk, Peter

AU - Löwenberg, Bob

AU - Ottone, Tiziana

AU - Noguera, Nelida I.

AU - Voso, Maria T.

AU - Paoloni, Francesca

AU - Fazi, Paola

AU - Ammatuna, Emanuele

AU - Huls, Gerwin

AU - Schuringa, Jan Jacob

AU - Rego, Eduardo M.

AU - Lucena-Araujo, Antonio R.

N1 - Funding Information: This investigation was supported by (CNPq; grant # 303479/2018‐3) and (FAPESP, Grant #2013/08135‐2). D.A.P.M. (Grant #2017/23117‐1), J.L.C.‐S. (Grant #2016/23191‐4) and I.W. (Grant #2015/09228‐0) received a fellowship from FAPESP. I.W and D.A.P‐M were sponsored by the Abel Tasman Talent Program of the Graduate School of Medical Sciences of the University of Groningen/University Medical Center Groningen, The Netherlands. Conselho Nacional de Desenvolvimento Científico e Tecnológico Fundação de Amparo à Pesquisa do Estado de São Paulo Funding information Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant/Award Number: 303479/2018-3; Fundação de Amparo à Pesquisa do Estado de São Paulo, Grant/Award Number: 2013/08135-2, 2015/09228-0, 2016/23191-4 and 2017/23117-1 Publisher Copyright: © 2022 British Society for Haematology and John Wiley & Sons Ltd.

PY - 2022/10/20

Y1 - 2022/10/20

N2 - Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA.

AB - Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA.

UR - http://www.scopus.com/inward/record.url?scp=85140053688&partnerID=8YFLogxK

U2 - 10.1111/bjh.18510

DO - 10.1111/bjh.18510

M3 - Article

AN - SCOPUS:85140053688

VL - 200

SP - 170

EP - 174

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 2

ER -

Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia

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