Case Report: Rare IKZF1 Gene Fusions Identified in Neonate with Congenital KMT2A-Rearranged Acute Lymphoblastic Leukemia

Laura N Eadie; Jacqueline A Rehn; James Breen; Michael P Osborn; Sophie Jessop; Charlotte E J Downes; Susan L Heatley; Barbara J McClure; David T Yeung; Tamas Revesz; Benjamin Saxon; Deborah L White

doi:10.3390/genes14020264

Case Report: Rare IKZF1 Gene Fusions Identified in Neonate with Congenital KMT2A-Rearranged Acute Lymphoblastic Leukemia

Genes (Basel). 2023 Jan 19;14(2):264. doi: 10.3390/genes14020264.

Authors

Laura N Eadie^{1

2}, Jacqueline A Rehn^{1

2}, James Breen^{2

3

4}, Michael P Osborn^{2

5

6

7

8}, Sophie Jessop^{5

7}, Charlotte E J Downes^{1

9}, Susan L Heatley^{1

2

5}, Barbara J McClure^{1

2}, David T Yeung^{1

2

6

8}, Tamas Revesz^{2

5

7}, Benjamin Saxon^{2

7

10}, Deborah L White^{1

2

5

6

9

11}

Affiliations

¹ Blood Cancer Program, Precision Cancer Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, SA 5000, Australia.
² Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
³ South Australian Genomics Centre (SAGC), Adelaide, SA 5000, Australia.
⁴ Robinson Research Institute, University of Adelaide, Adelaide, SA 5006, Australia.
⁵ Australian & New Zealand Children's Haematology/Oncology Group, Clayton, VIC 3168, Australia.
⁶ Australasian Leukaemia & Lymphoma Group, Richmond, VIC 3121, Australia.
⁷ Department of Haematology & Oncology, Women's & Children's Hospital, Adelaide, SA 5000, Australia.
⁸ Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
⁹ Faculty of Sciences, Engineering and Technology, University of Adelaide, Adelaide, SA 5000, Australia.
¹⁰ Clinical Services and Research Division, Australian Red Cross Blood Service, Adelaide, SA 5000, Australia.
¹¹ Australian Genomics Health Alliance, Parkville, VIC 3052, Australia.

Abstract

Chromosomal rearrangements involving the KMT2A gene occur frequently in acute lymphoblastic leukaemia (ALL). KMT2A-rearranged ALL (KMT2Ar ALL) has poor long-term survival rates and is the most common ALL subtype in infants less than 1 year of age. KMT2Ar ALL frequently occurs with additional chromosomal abnormalities including disruption of the IKZF1 gene, usually by exon deletion. Typically, KMT2Ar ALL in infants is accompanied by a limited number of cooperative le-sions. Here we report a case of aggressive infant KMT2Ar ALL harbouring additional rare IKZF1 gene fusions. Comprehensive genomic and transcriptomic analyses were performed on sequential samples. This report highlights the genomic complexity of this particular disease and describes the novel gene fusions IKZF1::TUT1 and KDM2A::IKZF1.

Keywords: IKZF1 translocation; KMT2A-rearranged ALL; case report; chromosomal abnormalities; congenital acute lymphoblastic leukemia; fusion gene; infant ALL; mRNA-sequencing.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Chromosome Aberrations
F-Box Proteins* / genetics
Gene Fusion
Genomics
Humans
Ikaros Transcription Factor / genetics
Infant
Infant, Newborn
Jumonji Domain-Containing Histone Demethylases / genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
Transcription Factors / genetics

Substances

Transcription Factors
IKZF1 protein, human
Ikaros Transcription Factor
KDM2A protein, human
F-Box Proteins
Jumonji Domain-Containing Histone Demethylases

Grants and funding

L.N.E. receives fellowship funding from the Peter Nelson Leukaemia Research Fellowship Fund, administered by the Cancer Council South Australia (grant number 022212). S.L.H. receives fellowship funding from The Kids’ Cancer Project (grant number 022214). D.T.Y. receives fellowship funding from the National Health and Medical Research Council (NHMRC; grant number 1146253). D.L.W. receives fellowship funding from the NHMRC (grant number 1160833) and the Cancer Council Beat Cancer Project (grant number 022213).