Publication

Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis

Folkerts, H., Wierenga, A. T., van den Heuvel, F. A., Woldhuis, R. R., Kluit, D. S., Jaques, J., Schuringa, J. J. & Vellenga, E., 29-May-2019, In : Cell death & disease. 10, 6, 12 p., 421.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Folkerts, H., Wierenga, A. T., van den Heuvel, F. A., Woldhuis, R. R., Kluit, D. S., Jaques, J., ... Vellenga, E. (2019). Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis. Cell death & disease, 10(6), [421]. https://doi.org/10.1038/s41419-019-1648-4

Author

Folkerts, Hendrik ; Wierenga, Albertus T ; van den Heuvel, Fiona A ; Woldhuis, Roy R ; Kluit, Darlyne S ; Jaques, Jennifer ; Schuringa, Jan Jacob ; Vellenga, Edo. / Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis. In: Cell death & disease. 2019 ; Vol. 10, No. 6.

Harvard

Folkerts, H, Wierenga, AT, van den Heuvel, FA, Woldhuis, RR, Kluit, DS, Jaques, J, Schuringa, JJ & Vellenga, E 2019, 'Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis' Cell death & disease, vol. 10, no. 6, 421. https://doi.org/10.1038/s41419-019-1648-4

Standard

Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis. / Folkerts, Hendrik; Wierenga, Albertus T; van den Heuvel, Fiona A; Woldhuis, Roy R; Kluit, Darlyne S; Jaques, Jennifer; Schuringa, Jan Jacob; Vellenga, Edo.

In: Cell death & disease, Vol. 10, No. 6, 421, 29.05.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Folkerts H, Wierenga AT, van den Heuvel FA, Woldhuis RR, Kluit DS, Jaques J et al. Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis. Cell death & disease. 2019 May 29;10(6). 421. https://doi.org/10.1038/s41419-019-1648-4


BibTeX

@article{72cfc47176ce4022a2e3ff8bd4fc73fe,
title = "Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis",
abstract = "Vacuole membrane protein (VMP1) is a putative autophagy protein, which together with Beclin-1 acts as a molecular switch in activating autophagy. In the present study the role of VMP1 was analysed in CD34+ cells of cord blood (CB) and primary acute myeloid leukemia (AML) cells and cell lines. An increased expression of VMP1 was observed in a subset of AML patients. Functional studies in normal CB CD34+ cells indicated that inhibiting VMP1 expression reduced autophagic-flux, coinciding with reduced expansion of hematopoietic stem and progenitor cells (HSPC), delayed differentiation, increased apoptosis and impaired in vivo engraftment. Comparable results were observed in leukemic cell lines and primary AML CD34+ cells. Ultrastructural analysis indicated that leukemic cells overexpressing VMP1 displayed a reduced number of mitochondrial structures, while the number of lysosomal degradation structures was increased. The overexpression of VMP1 did not affect cell proliferation and differentiation, but increased autophagic-flux and improved mitochondrial quality, which coincided with an increased threshold for venetoclax-induced loss of mitochondrial outer membrane permeabilization (MOMP) and apoptosis. In conclusion, our data indicate that in leukemic cells high VMP1 is involved with mitochondrial quality control.",
author = "Hendrik Folkerts and Wierenga, {Albertus T} and {van den Heuvel}, {Fiona A} and Woldhuis, {Roy R} and Kluit, {Darlyne S} and Jennifer Jaques and Schuringa, {Jan Jacob} and Edo Vellenga",
year = "2019",
month = "5",
day = "29",
doi = "10.1038/s41419-019-1648-4",
language = "English",
volume = "10",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "6",

}

RIS

TY - JOUR

T1 - Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis

AU - Folkerts, Hendrik

AU - Wierenga, Albertus T

AU - van den Heuvel, Fiona A

AU - Woldhuis, Roy R

AU - Kluit, Darlyne S

AU - Jaques, Jennifer

AU - Schuringa, Jan Jacob

AU - Vellenga, Edo

PY - 2019/5/29

Y1 - 2019/5/29

N2 - Vacuole membrane protein (VMP1) is a putative autophagy protein, which together with Beclin-1 acts as a molecular switch in activating autophagy. In the present study the role of VMP1 was analysed in CD34+ cells of cord blood (CB) and primary acute myeloid leukemia (AML) cells and cell lines. An increased expression of VMP1 was observed in a subset of AML patients. Functional studies in normal CB CD34+ cells indicated that inhibiting VMP1 expression reduced autophagic-flux, coinciding with reduced expansion of hematopoietic stem and progenitor cells (HSPC), delayed differentiation, increased apoptosis and impaired in vivo engraftment. Comparable results were observed in leukemic cell lines and primary AML CD34+ cells. Ultrastructural analysis indicated that leukemic cells overexpressing VMP1 displayed a reduced number of mitochondrial structures, while the number of lysosomal degradation structures was increased. The overexpression of VMP1 did not affect cell proliferation and differentiation, but increased autophagic-flux and improved mitochondrial quality, which coincided with an increased threshold for venetoclax-induced loss of mitochondrial outer membrane permeabilization (MOMP) and apoptosis. In conclusion, our data indicate that in leukemic cells high VMP1 is involved with mitochondrial quality control.

AB - Vacuole membrane protein (VMP1) is a putative autophagy protein, which together with Beclin-1 acts as a molecular switch in activating autophagy. In the present study the role of VMP1 was analysed in CD34+ cells of cord blood (CB) and primary acute myeloid leukemia (AML) cells and cell lines. An increased expression of VMP1 was observed in a subset of AML patients. Functional studies in normal CB CD34+ cells indicated that inhibiting VMP1 expression reduced autophagic-flux, coinciding with reduced expansion of hematopoietic stem and progenitor cells (HSPC), delayed differentiation, increased apoptosis and impaired in vivo engraftment. Comparable results were observed in leukemic cell lines and primary AML CD34+ cells. Ultrastructural analysis indicated that leukemic cells overexpressing VMP1 displayed a reduced number of mitochondrial structures, while the number of lysosomal degradation structures was increased. The overexpression of VMP1 did not affect cell proliferation and differentiation, but increased autophagic-flux and improved mitochondrial quality, which coincided with an increased threshold for venetoclax-induced loss of mitochondrial outer membrane permeabilization (MOMP) and apoptosis. In conclusion, our data indicate that in leukemic cells high VMP1 is involved with mitochondrial quality control.

U2 - 10.1038/s41419-019-1648-4

DO - 10.1038/s41419-019-1648-4

M3 - Article

VL - 10

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 6

M1 - 421

ER -

ID: 84189590