Fusion Genes in Acute Leukemias: Genetic Characterization of Rare Cases

Overview

Journal Front Oncol

Specialty Oncology

Date 2024 Apr 4

PMID 38571499

Authors

Marta Brunetti

Kristin Andersen

Signe Spetalen

Andrea Lenartova

Liv Toril Nygard Osnes

Helen Valerhaugen

Sverre Heim

Francesca Micci

Affiliations

Soon will be listed here.

Abstract

Introduction: Alterations of the gene (9q34) are recurrent in acute leukemias. Rearrangements of chromosomal band 9q34 targeting this locus can be karyotypically distinct, for example t(6;9)(p22;q34)/, or cryptic, in which case no visible change of 9q34 is seen by chromosome banding.

Methods: We examined 9 cases of acute leukemia with rearrangement by array Comparative Genomic Hybridization (aCGH), reverse-transcription polymerase chain reaction (RT-PCR), and cycle sequencing/Sanger sequencing to detect which fusion genes had been generated.

Results: The chimeras ::, ::, and :: were found, only the first of which can be readily detected by karyotyping.

Discussion: The identification of a specific rearrangement is fundamental in the management of these patients, i.e., AMLs with are classified as an adverse risk group and might be considered for allogenic transplant. Genome- and/or transcriptome-based next generation sequencing (NGS) techniques can be used to screen for these fusions, but we hereby present an alternative, step-wise procedure to detect these rearrangements.

References

Schoumans J, Suela J, Hastings R, Muehlematter D, Rack K, van den Berg E . Guidelines for genomic array analysis in acquired haematological neoplastic disorders. Genes Chromosomes Cancer. 2016; 55(5):480-91. DOI: 10.1002/gcc.22350. View

Clarke S, OReilly J, Romeo G, Cooney J . NUP214-ABL1 positive T-cell acute lymphoblastic leukemia patient shows an initial favorable response to imatinib therapy post relapse. Leuk Res. 2011; 35(7):e131-3. DOI: 10.1016/j.leukres.2011.03.025. View

Ballerini P, Landman-Parker J, Cayuela J, Asnafi V, Labopin M, Gandemer V . Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome. Haematologica. 2008; 93(11):1658-65. DOI: 10.3324/haematol.13291. View

Van Vlierberghe P, Ferrando A . The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest. 2012; 122(10):3398-406. PMC: 3461904. DOI: 10.1172/JCI61269. View

von Lindern M, Fornerod M, Van Baal S, Jaegle M, De Wit T, Buijs A . The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol. 1992; 12(4):1687-97. PMC: 369612. DOI: 10.1128/mcb.12.4.1687-1697.1992. View

Quintas-Cardama A, Tong W, Manshouri T, Vega F, Lennon P, Cools J . Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. Leukemia. 2008; 22(6):1117-24. DOI: 10.1038/leu.2008.80. View

Kaplan H, Jin R, Bifulco C, Scanlan J, Corwin D . PCM1-JAK2 Fusion Tyrosine Kinase Gene-Related Neoplasia: A Systematic Review of the Clinical Literature. Oncologist. 2022; 27(8):e661-e670. PMC: 9355817. DOI: 10.1093/oncolo/oyac072. View

Soekarman D, von Lindern M, Daenen S, de Jong B, Fonatsch C, Heinze B . The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. Blood. 1992; 79(11):2990-7. View

Kasbekar M, Nardi V, Dal Cin P, Brunner A, Burke M, Chen Y . Targeted FGFR inhibition results in a durable remission in an FGFR1-driven myeloid neoplasm with eosinophilia. Blood Adv. 2020; 4(13):3136-3140. PMC: 7362377. DOI: 10.1182/bloodadvances.2020002308. View

10.

Quist-Paulsen P, Toft N, Heyman M, Abrahamsson J, Griskevicius L, Hallbook H . T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol. Leukemia. 2019; 34(2):347-357. DOI: 10.1038/s41375-019-0598-2. View

11.

Graux C, Cools J, Melotte C, Quentmeier H, Ferrando A, Levine R . Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet. 2004; 36(10):1084-9. DOI: 10.1038/ng1425. View

12.

Olshen A, Venkatraman E, Lucito R, Wigler M . Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics. 2004; 5(4):557-72. DOI: 10.1093/biostatistics/kxh008. View

13.

Kent W . BLAT--the BLAST-like alignment tool. Genome Res. 2002; 12(4):656-64. PMC: 187518. DOI: 10.1101/gr.229202. View

14.

Mikhail F, Biegel J, Cooley L, Dubuc A, Hirsch B, Horner V . Technical laboratory standards for interpretation and reporting of acquired copy-number abnormalities and copy-neutral loss of heterozygosity in neoplastic disorders: a joint consensus recommendation from the American College of Medical Genetics and.... Genet Med. 2019; 21(9):1903-1916. DOI: 10.1038/s41436-019-0545-7. View

15.

Gorello P, La Starza R, Di Giacomo D, Messina M, Puzzolo M, Crescenzi B . SQSTM1-NUP214: a new gene fusion in adult T-cell acute lymphoblastic leukemia. Haematologica. 2010; 95(12):2161-3. PMC: 2995577. DOI: 10.3324/haematol.2010.029769. View

16.

Altschul S, Gish W, Miller W, Myers E, Lipman D . Basic local alignment search tool. J Mol Biol. 1990; 215(3):403-10. DOI: 10.1016/S0022-2836(05)80360-2. View

17.

Fleischmann M, Schnetzke U, Hochhaus A, Scholl S . Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives. Cancers (Basel). 2021; 13(22). PMC: 8616498. DOI: 10.3390/cancers13225722. View

18.

Cooley L, Lebo M, Li M, Slovak M, Wolff D . American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders. Genet Med. 2013; 15(6):484-94. DOI: 10.1038/gim.2013.49. View

19.

Sanden C, Ageberg M, Petersson J, Lennartsson A, Gullberg U . Forced expression of the DEK-NUP214 fusion protein promotes proliferation dependent on upregulation of mTOR. BMC Cancer. 2013; 13:440. PMC: 3849736. DOI: 10.1186/1471-2407-13-440. View

20.

Strati P, Tang G, Duose D, Mallampati S, Luthra R, Patel K . Myeloid/lymphoid neoplasms with FGFR1 rearrangement. Leuk Lymphoma. 2017; 59(7):1672-1676. DOI: 10.1080/10428194.2017.1397663. View