Characterization of Pediatric Acute Myeloid Leukemia With t(7;12)(q36;p13)

Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is a recurrent translocation in AML in infants or very young children and was recently included in the World Health Organization (WHO) Classification of Hematolymphoid Tumors. AML with t(7;12) is reported to involve MNX1 and ETV6 signaling; however, the mechanism of leukemogenesis is not well understood, and the presence of MNX1::ETV6 fusion transcripts has only been confirmed in approximately 50% of cases. In contrast, high expression of MNX1 has been seen in all investigated cases. In this study, we investigated the clinical as well as biological characteristics of 12 pediatric AML with t(7;12) and performed whole transcriptome (WTS) and whole genome sequencing (WGS) on six of these. There was no significant difference in event-free survival or overall survival of these t(7;12) AML patients compared with other AML in the same age group. Interestingly, WTS identified several fusion transcripts involving ETV6 but not together with MNX1. WGS identified the genomic breakpoints and revealed that a common fusion partner on chromosome 7 was NOM1. Principal component analysis (PCA) of the WTS data showed that all t(7;12) AML cases cluster together, separate from all other pediatric AML subtypes; all cases had high expression of MNX1, MNX1-AS1, and MNX1-AS2. Hence, t(7;12) AML, despite expressing different fusion transcripts and with varying translocation breakpoints, constitutes a phenotypically homogenous subgroup. This underlines that the leukemia-driving event most likely is ectopic expression of MNX1 and that this therefore should be the defining Classifying criteria of this type of AML.

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Publication Details

Journal
Genes Chromosomes and Cancer
Published
2024-11-01
DOI
https://doi.org/10.1002/gcc.70003
Citations
4
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
1.82

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Characterization of Pediatric Acute Myeloid Leukemia With t(7;12)(q36;p13)

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Characterization of Pediatric Acute Myeloid Leukemia With t(7;12)(q36;p13)

Bernward Zeller, Zhanna Kovalova, Linda Fogelstrand, Nira Arad‐Cohen, Gertjan J.L. Kaspers, Daniel KL Cheuk, Ulrika Norén‐Nyström, Lars Palmqvist, Helene Sjögren, Kadri Saks, Jonas Abrahamsson, Anna Staffas, Barbara De Moerloose, Henrik Hasle, Kirsi Jahnukainen, Ramunė Pasaulienė, Ahmed Waraky, José María Fernández Navarro, Anders Östlund
article en
4 citations

Abstract

Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is a recurrent translocation in AML in infants or very young children and was recently included in the World Health Organization (WHO) Classification of Hematolymphoid Tumors. AML with t(7;12) is reported to involve MNX1 and ETV6 signaling; however, the mechanism of leukemogenesis is not well understood, and the presence of MNX1::ETV6 fusion transcripts has only been confirmed in approximately 50% of cases. In contrast, high expression of MNX1 has been seen in all investigated cases. In this study, we investigated the clinical as well as biological characteristics of 12 pediatric AML with t(7;12) and performed whole transcriptome (WTS) and whole genome sequencing (WGS) on six of these. There was no significant difference in event-free survival or overall survival of these t(7;12) AML patients compared with other AML in the same age group. Interestingly, WTS identified several fusion transcripts involving ETV6 but not together with MNX1. WGS identified the genomic breakpoints and revealed that a common fusion partner on chromosome 7 was NOM1. Principal component analysis (PCA) of the WTS data showed that all t(7;12) AML cases cluster together, separate from all other pediatric AML subtypes; all cases had high expression of MNX1, MNX1-AS1, and MNX1-AS2. Hence, t(7;12) AML, despite expressing different fusion transcripts and with varying translocation breakpoints, constitutes a phenotypically homogenous subgroup. This underlines that the leukemia-driving event most likely is ectopic expression of MNX1 and that this therefore should be the defining Classifying criteria of this type of AML.

Genes Chromosomes and CancerVol. 63(11)
Oslo University Hospital (NO), University of Helsinki (FI), Vilnius University (LT), Helsinki University Hospital (FI), Sahlgrenska University Hospital (SE), Ghent University Hospital (BE), Rambam Health Care Campus (IL), Aarhus University Hospital (DK), Hospital Universitari i Politècnic La Fe (ES), Helsinki Children's Hospital (FI), Emma Kinderziekenhuis (NL), Tallinn Health Care College (EE), Children's Clinical University Hospital (LV), Princess Máxima Center (NL), Amsterdam University Medical Centers (NL), Vrije Universiteit Amsterdam (NL), University of Gothenburg (SE), University of Hong Kong (HK), Umeå University (SE)
Västra Götalandsregionen, Cancerfonden, Stiftelsen Assar Gabrielssons Fond, Sahlgrenska Universitetssjukhuset, Göteborgs Universitet, Barncancerfonden, Science for Life Laboratory, Sahlgrenska Akademin
Good health and well-being
Openalex Percentile: Top 14%
Acute Myeloid Leukemia Research
1.82
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