Analysis of rare driving events in pediatric acute myeloid
leukemia

J 2023

Analysis of rare driving events in pediatric acute myeloid leukemia

NOORT, Sanne, van Oosterwijk JOLIEKE, Jing MA, Elizabeth A R GARFINKLE, Stephanie NANCE et. al.

Basic information

Original name

Analysis of rare driving events in pediatric acute myeloid leukemia

Authors

NOORT, Sanne, van Oosterwijk JOLIEKE, Jing MA, Elizabeth A R GARFINKLE, Stephanie NANCE, Michael WALSH, Guangchun SONG, Dirk REINHARDT, Martina PIGAZZI, Franco LOCATELLI, Henrik HASLE, Jonas ABRAHAMSSON, Marie JAROŠOVÁ (203 Czech Republic, belonging to the institution), Charikleia KELAIDI, Sophia POLYCHRONOPOULOU, Marry M VAN DEN HEUVEL-EIBRINK, Maarten FORNEROD, Tanja A GRUBER and C Michel ZWAAN (guarantor)

Edition

haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2023, 0390-6078

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Italy

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.100 in 2022

RIV identification code

RIV/00216224:14110/23:00131006

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3324/haematol.2021.280250

UT WoS

001000812400004

Keywords in English

pediatric acute myeloid leukemia; rare driving events

Abstract

V originále

Elucidating genetic aberrations in pediatric acute myeloid leukemia (AML) provides insight in biology and may impact on risk-group stratification and clinical outcome. This study aimed to detect such aberrations in a selected series of samples without known (cyto)genetic aberration using molecular profiling. A cohort of 161 patients was selected from various study groups: DCOG, BFM, SJCRH, NOPHO and AEIOP. Samples were analyzed using RNA sequencing (n=152), whole exome (n=135) and/or whole genome sequencing (n=100). In 70 of 156 patients (45%), of whom RNA sequencing or whole genome sequencing was available, rearrangements were detected, 22 of which were novel; five involving ERG rearrangements and four NPM1 rearrangements. ERG rearrangements showed self-renewal capacity in vitro, and a distinct gene expression pattern. Gene set enrichment analysis of this cluster showed upregulation of gene sets derived from Ewing sarcoma, which was confirmed comparing gene expression profiles of AML and Ewing sarcoma. Furthermore, NPM1-rearranged cases showed cytoplasmic NPM1 localization and revealed HOXA/B gene overexpression, as described for NPM1 mutated cases. Single-gene mutations as identified in adult AML were rare. Patients had a median of 24 coding mutations (range, 7-159). Novel recurrent mutations were detected in UBTF (n=10), a regulator of RNA transcription. In 75% of patients an aberration with a prognostic impact could be detected. Therefore, we suggest these techniques need to become standard of care in diagnostics.

Citovat

NOORT, Sanne, van Oosterwijk JOLIEKE, Jing MA, Elizabeth A R GARFINKLE, Stephanie NANCE, Michael WALSH, Guangchun SONG, Dirk REINHARDT, Martina PIGAZZI, Franco LOCATELLI, Henrik HASLE, Jonas ABRAHAMSSON, Marie JAROŠOVÁ, Charikleia KELAIDI, Sophia POLYCHRONOPOULOU, Marry M VAN DEN HEUVEL-EIBRINK, Maarten FORNEROD, Tanja A GRUBER and C Michel ZWAAN. Analysis of rare driving events in pediatric acute myeloid leukemia. haematologica. PAVIA: FERRATA STORTI FOUNDATION, 2023, vol. 108, No 1, p. 48-60. ISSN 0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2021.280250.

@article{2292759,
   author = {Noort, Sanne and Jolieke, van Oosterwijk and Ma, Jing and Garfinkle, Elizabeth A R and Nance, Stephanie and Walsh, Michael and Song, Guangchun and Reinhardt, Dirk and Pigazzi, Martina and Locatelli, Franco and Hasle, Henrik and Abrahamsson, Jonas and Jarošová, Marie and Kelaidi, Charikleia and Polychronopoulou, Sophia and van den HeuvelandEibrink, Marry M and Fornerod, Maarten and Gruber, Tanja A and Zwaan, C Michel},
   article_location = {PAVIA},
   article_number = {1},
   doi = {http://dx.doi.org/10.3324/haematol.2021.280250},
   keywords = {pediatric acute myeloid leukemia; rare driving events},
   language = {eng},
   issn = {0390-6078},
   journal = {haematologica},
   title = {Analysis of rare driving events in pediatric acute myeloid leukemia},
   url = {https://www.haematologica.org/article/view/haematol.2021.280250},
   volume = {108},
   year = {2023}
}

TY  - JOUR
ID  - 2292759
AU  - Noort, Sanne - Jolieke, van Oosterwijk - Ma, Jing - Garfinkle, Elizabeth A R - Nance, Stephanie - Walsh, Michael - Song, Guangchun - Reinhardt, Dirk - Pigazzi, Martina - Locatelli, Franco - Hasle, Henrik - Abrahamsson, Jonas - Jarošová, Marie - Kelaidi, Charikleia - Polychronopoulou, Sophia - van den Heuvel-Eibrink, Marry M - Fornerod, Maarten - Gruber, Tanja A - Zwaan, C Michel
PY  - 2023
TI  - Analysis of rare driving events in pediatric acute myeloid leukemia
JF  - haematologica
VL  - 108
IS  - 1
SP  - 48-60
EP  - 48-60
PB  - FERRATA STORTI FOUNDATION
SN  - 03906078
KW  - pediatric acute myeloid leukemia
KW  - rare driving events
UR  - https://www.haematologica.org/article/view/haematol.2021.280250
N2  - Elucidating genetic aberrations in pediatric acute myeloid leukemia (AML) provides insight in biology and may impact on risk-group stratification and clinical outcome. This study aimed to detect such aberrations in a selected series of samples without known (cyto)genetic aberration using molecular profiling. A cohort of 161 patients was selected from various study groups: DCOG, BFM, SJCRH, NOPHO and AEIOP. Samples were analyzed using RNA sequencing (n=152), whole exome (n=135) and/or whole genome sequencing (n=100). In 70 of 156 patients (45%), of whom RNA sequencing or whole genome sequencing was available, rearrangements were detected, 22 of which were novel; five involving ERG rearrangements and four NPM1 rearrangements. ERG rearrangements showed self-renewal capacity in vitro, and a distinct gene expression pattern. Gene set enrichment analysis of this cluster showed upregulation of gene sets derived from Ewing sarcoma, which was confirmed comparing gene expression profiles of AML and Ewing sarcoma. Furthermore, NPM1-rearranged cases showed cytoplasmic NPM1 localization and revealed HOXA/B gene overexpression, as described for NPM1 mutated cases. Single-gene mutations as identified in adult AML were rare. Patients had a median of 24 coding mutations (range, 7-159). Novel recurrent mutations were detected in UBTF (n=10), a regulator of RNA transcription. In 75% of patients an aberration with a prognostic impact could be detected. Therefore, we suggest these techniques need to become standard of care in diagnostics.
ER  -

NOORT, Sanne, van Oosterwijk JOLIEKE, Jing MA, Elizabeth A R GARFINKLE, Stephanie NANCE, Michael WALSH, Guangchun SONG, Dirk REINHARDT, Martina PIGAZZI, Franco LOCATELLI, Henrik HASLE, Jonas ABRAHAMSSON, Marie JAROŠOVÁ, Charikleia KELAIDI, Sophia POLYCHRONOPOULOU, Marry M VAN DEN HEUVEL-EIBRINK, Maarten FORNEROD, Tanja A GRUBER and C Michel ZWAAN. Analysis of rare driving events in pediatric acute myeloid leukemia. \textit{haematologica}. PAVIA: FERRATA STORTI FOUNDATION, 2023, vol.~108, No~1, p.~48-60. ISSN~0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2021.280250.

Detailed Information on Publication Record