Microrna-106b∼25 Cluster Is Involved in Relapsed MLL-Rearranged Pediatric AML

Lonneke Verboon; Maarten Fornerod; Askar Obulkasim; Edwin Sonneveld; André Baruchel; Jan Trka; Dirk Reinhardt; Rob Pieters; Jacqueline Cloos; Gertjan J.L. Kaspers; Jan Henning Klusmann; C. Michel Zwaan; M van den Heuvel-Eibrink

doi:10.1182/blood.V124.21.1038.1038

Microrna-106b∼25 Cluster Is Involved in Relapsed MLL-Rearranged Pediatric AML

Lonneke Verboon, Maarten Fornerod, Askar Obulkasim, Edwin Sonneveld, André Baruchel, Jan Trka, Dirk Reinhardt, Rob Pieters, Jacqueline Cloos, Gertjan J.L. Kaspers, Jan Henning Klusmann, C. Michel Zwaan, M van den Heuvel-Eibrink

Pediatrics

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

Abstract

Mixed lineage leukemia (MLL) rearrangements represent about 20% of pediatric acute myeloid leukemia
(AML) cases. Survival rates have increased over the past decades due to intensified chemotherapy
protocols and improved supportive care. Still, approximately 30-40% will relapse during or after therapy.
The role of microRNAs (miRNAs) in leukemogenesis of MLL-rearranged AML, especially towards the
development of relapse is unknown. To determine whether specific miRNAs are involved in relapse
development, we performed miRNA profiling, using TaqMan Low Density Array (TLDA) in pediatric AML
with a special focus on MLL-rearranged cases. First, we compared miRNA profiles of de novo pediatric
AML patients that relapsed with those that did not relapse. Secondly, we did the same comparison, only
focussing on the MLL-rearranged subset. Third, we investigated the role of miRNAs in clonal evolution by
investigating the differential expression of 6 paired initial diagnosis-relapses MLL-rearranged AML cases.
An independent set of 6 paired initial diagnosis-relapse cases with MLL-rearrangements was used to confirm the identified miRNAs using single stemloop RT-qPCR.
[...]
Together, our data indicate that miR-106b-25 cluster may play an important role in relapse pediatric AML with MLL-rearrangements. Further research is warranted to identify the role of this cluster for clinical resistance and as treatment target.

Original language	English
Pages (from-to)	1038
Journal	Blood
Volume	124
Issue number	21
DOIs	https://doi.org/10.1182/blood.V124.21.1038.1038
Publication status	Published - 6 Dec 2014

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EMC MM-02-54-03

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10.1182/blood.V124.21.1038.1038

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@article{fcf6db7c675f47b997592f8ca411998a,

title = "Microrna-106b∼25 Cluster Is Involved in Relapsed MLL-Rearranged Pediatric AML",

abstract = "Mixed lineage leukemia (MLL) rearrangements represent about 20% of pediatric acute myeloid leukemia(AML) cases. Survival rates have increased over the past decades due to intensified chemotherapyprotocols and improved supportive care. Still, approximately 30-40% will relapse during or after therapy.The role of microRNAs (miRNAs) in leukemogenesis of MLL-rearranged AML, especially towards thedevelopment of relapse is unknown. To determine whether specific miRNAs are involved in relapsedevelopment, we performed miRNA profiling, using TaqMan Low Density Array (TLDA) in pediatric AMLwith a special focus on MLL-rearranged cases. First, we compared miRNA profiles of de novo pediatricAML patients that relapsed with those that did not relapse. Secondly, we did the same comparison, onlyfocussing on the MLL-rearranged subset. Third, we investigated the role of miRNAs in clonal evolution byinvestigating the differential expression of 6 paired initial diagnosis-relapses MLL-rearranged AML cases.An independent set of 6 paired initial diagnosis-relapse cases with MLL-rearrangements was used to confirm the identified miRNAs using single stemloop RT-qPCR. [...]Together, our data indicate that miR-106b-25 cluster may play an important role in relapse pediatric AML with MLL-rearrangements. Further research is warranted to identify the role of this cluster for clinical resistance and as treatment target.",

author = "Lonneke Verboon and Maarten Fornerod and Askar Obulkasim and Edwin Sonneveld and Andr{\'e} Baruchel and Jan Trka and Dirk Reinhardt and Rob Pieters and Jacqueline Cloos and Kaspers, {Gertjan J.L.} and Klusmann, {Jan Henning} and Zwaan, {C. Michel} and {van den Heuvel-Eibrink}, M",

year = "2014",

month = dec,

day = "6",

doi = "10.1182/blood.V124.21.1038.1038",

language = "English",

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pages = "1038",

journal = "Blood",

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TY - JOUR

T1 - Microrna-106b∼25 Cluster Is Involved in Relapsed MLL-Rearranged Pediatric AML

AU - Verboon, Lonneke

AU - Fornerod, Maarten

AU - Obulkasim, Askar

AU - Sonneveld, Edwin

AU - Baruchel, André

AU - Trka, Jan

AU - Reinhardt, Dirk

AU - Pieters, Rob

AU - Cloos, Jacqueline

AU - Kaspers, Gertjan J.L.

AU - Klusmann, Jan Henning

AU - Zwaan, C. Michel

AU - van den Heuvel-Eibrink, M

PY - 2014/12/6

Y1 - 2014/12/6

N2 - Mixed lineage leukemia (MLL) rearrangements represent about 20% of pediatric acute myeloid leukemia(AML) cases. Survival rates have increased over the past decades due to intensified chemotherapyprotocols and improved supportive care. Still, approximately 30-40% will relapse during or after therapy.The role of microRNAs (miRNAs) in leukemogenesis of MLL-rearranged AML, especially towards thedevelopment of relapse is unknown. To determine whether specific miRNAs are involved in relapsedevelopment, we performed miRNA profiling, using TaqMan Low Density Array (TLDA) in pediatric AMLwith a special focus on MLL-rearranged cases. First, we compared miRNA profiles of de novo pediatricAML patients that relapsed with those that did not relapse. Secondly, we did the same comparison, onlyfocussing on the MLL-rearranged subset. Third, we investigated the role of miRNAs in clonal evolution byinvestigating the differential expression of 6 paired initial diagnosis-relapses MLL-rearranged AML cases.An independent set of 6 paired initial diagnosis-relapse cases with MLL-rearrangements was used to confirm the identified miRNAs using single stemloop RT-qPCR. [...]Together, our data indicate that miR-106b-25 cluster may play an important role in relapse pediatric AML with MLL-rearrangements. Further research is warranted to identify the role of this cluster for clinical resistance and as treatment target.

AB - Mixed lineage leukemia (MLL) rearrangements represent about 20% of pediatric acute myeloid leukemia(AML) cases. Survival rates have increased over the past decades due to intensified chemotherapyprotocols and improved supportive care. Still, approximately 30-40% will relapse during or after therapy.The role of microRNAs (miRNAs) in leukemogenesis of MLL-rearranged AML, especially towards thedevelopment of relapse is unknown. To determine whether specific miRNAs are involved in relapsedevelopment, we performed miRNA profiling, using TaqMan Low Density Array (TLDA) in pediatric AMLwith a special focus on MLL-rearranged cases. First, we compared miRNA profiles of de novo pediatricAML patients that relapsed with those that did not relapse. Secondly, we did the same comparison, onlyfocussing on the MLL-rearranged subset. Third, we investigated the role of miRNAs in clonal evolution byinvestigating the differential expression of 6 paired initial diagnosis-relapses MLL-rearranged AML cases.An independent set of 6 paired initial diagnosis-relapse cases with MLL-rearrangements was used to confirm the identified miRNAs using single stemloop RT-qPCR. [...]Together, our data indicate that miR-106b-25 cluster may play an important role in relapse pediatric AML with MLL-rearrangements. Further research is warranted to identify the role of this cluster for clinical resistance and as treatment target.

UR - https://www.sciencedirect.com/science/article/pii/S0006497119699751

UR - https://www.researchgate.net/publication/336385091_Microrna-106b25_Cluster_Is_Involved_in_Relapsed_MLL-Rearranged_Pediatric_AML

U2 - 10.1182/blood.V124.21.1038.1038

DO - 10.1182/blood.V124.21.1038.1038

M3 - Article

SN - 0006-4971

VL - 124

SP - 1038

JO - Blood

JF - Blood

IS - 21

ER -

Microrna-106b∼25 Cluster Is Involved in Relapsed MLL-Rearranged Pediatric AML

Abstract

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MicroRNA-106b similar to 25 cluster is upregulated in relapsed MLL-rearranged pediatric acute myeloid leukemia

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