Clinical significance of mitochondrial DNA content in acute promyelocytic leukaemia

Diego A. Pereira-Martins; Juan L. Coelho-Silva; Isabel Weinhauser; Pedro L. Franca-Neto; Douglas R. Silveira; Cesar Ortiz; Amanda Moreira-Aguiar; Marinus M. Lima; Luisa C. Koury; Raul A. de Melo; Ana B. Gloria; 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 Lowenberg; Tiziana Ottone; Nelida 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 Weinhauser, Pedro L. Franca-Neto, Douglas R. Silveira, Cesar Ortiz, Amanda Moreira-Aguiar, Marinus M. Lima, Luisa C. Koury, Raul A. de Melo, Ana B. Gloria, 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 Lowenberg, Tiziana Ottone, Nelida 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

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
Early online date	20-Oct-2022
DOIs	https://doi.org/10.1111/bjh.18510
Publication status	Published - Jan-2023

Keywords

anthracycline-based chemotherapy
ATRA
mtDNA content
oxidative phosphorylation
RETINOIC ACID
ARSENIC TRIOXIDE
RAR-ALPHA
RISK

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Pereira-Martins, D. A., Coelho-Silva, J. L., Weinhauser, I., Franca-Neto, P. L., Silveira, D. R., Ortiz, C., Moreira-Aguiar, A., Lima, M. M., Koury, L. C., de Melo, R. A., Gloria, A. B., Fagundes, E. M., Lino, B. K., Pagnano, K., Bittencourt, R., Nunes, E., Traina, F., Figueiredo-Pontes, L., Keating, A., ... Lucena-Araujo, A. R. (2023). 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{0b40bc6bd1c1493dbf888de8504519e7,

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.",

keywords = "anthracycline-based chemotherapy, ATRA, mtDNA content, oxidative phosphorylation, RETINOIC ACID, ARSENIC TRIOXIDE, RAR-ALPHA, RISK",

author = "Pereira-Martins, {Diego A.} and Coelho-Silva, {Juan L.} and Isabel Weinhauser and Franca-Neto, {Pedro L.} and Silveira, {Douglas R.} and Cesar Ortiz and Amanda Moreira-Aguiar and Lima, {Marinus M.} and Koury, {Luisa C.} and {de Melo}, {Raul A.} and Gloria, {Ana B.} and Fagundes, {Evandro M.} 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 Lowenberg and Tiziana Ottone and Nelida Noguera and Voso, {Maria T.} and Francesca Paoloni and Paola Fazi and Emanuele Ammatuna and Gerwin Huls and Schuringa, {Jan Jacob} and Rego, {Eduardo M.} and Lucena-Araujo, {Antonio R.}",

year = "2023",

month = jan,

doi = "10.1111/bjh.18510",

language = "English",

volume = "200",

pages = "170--174",

journal = "British Journal of Haematology",

issn = "0007-1048",

publisher = "Wiley",

number = "2",

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Pereira-Martins, DA, Coelho-Silva, JL, Weinhauser, I, Franca-Neto, PL, Silveira, DR, Ortiz, C, Moreira-Aguiar, A, Lima, MM, Koury, LC, de Melo, RA, Gloria, 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, Lowenberg, B, Ottone, T, Noguera, N, Voso, MT, Paoloni, F, Fazi, P, Ammatuna, E , Huls, G , Schuringa, JJ, Rego, EM & Lucena-Araujo, AR 2023, '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 - Weinhauser, Isabel

AU - Franca-Neto, Pedro L.

AU - Silveira, Douglas R.

AU - Ortiz, Cesar

AU - Moreira-Aguiar, Amanda

AU - Lima, Marinus M.

AU - Koury, Luisa C.

AU - de Melo, Raul A.

AU - Gloria, 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 - Lowenberg, Bob

AU - Ottone, Tiziana

AU - Noguera, Nelida

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.

PY - 2023/1

Y1 - 2023/1

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.

KW - anthracycline-based chemotherapy

KW - ATRA

KW - mtDNA content

KW - oxidative phosphorylation

KW - RETINOIC ACID

KW - ARSENIC TRIOXIDE

KW - RAR-ALPHA

KW - RISK

U2 - 10.1111/bjh.18510

DO - 10.1111/bjh.18510

M3 - Article

SN - 0007-1048

VL - 200

SP - 170

EP - 174

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 2

ER -