Recurrent Novel Translocations in B-Lymphoblastic Leukemia/Lymphoma

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Aug 1

PMID 35912172

Authors

Yanglan Fang

Man Wang

Shuhong Hu

Tanzhen Wang

Yujie Liu

Jinyan Xiao

Yiming Cai

Ying Wang

Huiying Qiu

Xiaowen Tang

Suning Chen

Depei Wu

Yang Xu

Tianhui Liu

Affiliations

Soon will be listed here.

Abstract

Translocations involving the immunoglobulin heavy chain () locus are common abnormalities in B-lymphoblastic leukemia/lymphoma (B-ALL) and multiple myeloma. These rearrangements result in a juxtaposition of enhancers to the vicinity of oncogenes, such as and , leading to the upregulation of oncogenes. Here, we identified recurrent novel translocations in three B-ALL patients by transcriptome sequencing. Noncoding exon 1 of was translocated to different sites of the gene, resulting in transcripts of , , and . However, a high expression level of truncated was observed in the patients compared with healthy donors, which might be related to the aggressive clinical course and inferior outcome. In summary, we described recurrent novel translocations with high expression levels of , which may contribute to the guidelines for clinical diagnosis and treatment.

Citing Articles

Immune signature of gene expression pattern shared by autism spectrum disorder and Huntington's disease.

Liu H, Bai Q, Wang X, Jin Y, Ju X, Lu C IBRO Neurosci Rep. 2024; 17:311-319.

PMID: 39398347 PMC: 11471255. DOI: 10.1016/j.ibneur.2024.09.004.

References

Akasaka T, Balasas T, Russell L, Sugimoto K, Majid A, Walewska R . Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood. 2006; 109(8):3451-61. DOI: 10.1182/blood-2006-08-041012. View

Hunger S, Mullighan C . Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2015; 373(16):1541-52. DOI: 10.1056/NEJMra1400972. View

Willis T, Dyer M . The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies. Blood. 2000; 96(3):808-22. View

Han J, Akira S, Calame K, Beutler B, Selsing E, Imanishi-Kari T . Class switch recombination and somatic hypermutation in early mouse B cells are mediated by B cell and Toll-like receptors. Immunity. 2007; 27(1):64-75. PMC: 2082107. DOI: 10.1016/j.immuni.2007.05.018. View

Schmah J, Fedders B, Panzer-Grumayer R, Fischer S, Zimmermann M, Dagdan E . Molecular characterization of acute lymphoblastic leukemia with high CRLF2 gene expression in childhood. Pediatr Blood Cancer. 2017; 64(10). DOI: 10.1002/pbc.26539. View

Lu E, Wolfreys F, Muppidi J, Xu Y, Cyster J . S-Geranylgeranyl-L-glutathione is a ligand for human B cell-confinement receptor P2RY8. Nature. 2019; 567(7747):244-248. PMC: 6640153. DOI: 10.1038/s41586-019-1003-z. View

Mullighan C . Genomic characterization of childhood acute lymphoblastic leukemia. Semin Hematol. 2013; 50(4):314-24. PMC: 3848419. DOI: 10.1053/j.seminhematol.2013.10.001. View

Li T, Xue Y, Wu Y, Pan J . FISH studies identify the i(20q-) anomaly as a der(20)del(20)(q11q13)idic(20)(p11). Genes Chromosomes Cancer. 2006; 45(6):536-9. DOI: 10.1002/gcc.20313. View

Muppidi J, Lu E, Cyster J . The G protein-coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination. J Exp Med. 2015; 212(13):2213-22. PMC: 4689170. DOI: 10.1084/jem.20151250. View

10.

Fujiwara S, Yamashita Y, Choi Y, Watanabe H, Kurashina K, Soda M . Transforming activity of purinergic receptor P2Y, G protein coupled, 8 revealed by retroviral expression screening. Leuk Lymphoma. 2007; 48(5):978-86. DOI: 10.1080/10428190701225882. View

11.

Adrian K, Bernhard M, Breitinger H, Ogilvie A . Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells. Biochim Biophys Acta. 2000; 1492(1):127-38. DOI: 10.1016/s0167-4781(00)00094-4. View

12.

Russell L, De Castro D, Griffiths M, Telford N, Bernard O, Panzer-Grumayer R . A novel translocation, t(14;19)(q32;p13), involving IGH@ and the cytokine receptor for erythropoietin. Leukemia. 2008; 23(3):614-7. DOI: 10.1038/leu.2008.250. View

13.

Xiao A, Jia Y, Baughn L, Pearce K, Pitel B, Aster J . rearrangement in myeloid neoplasms. Haematologica. 2020; 105(6):e315-e317. PMC: 7271583. DOI: 10.3324/haematol.2020.246744. View

14.

Russell L, Enshaei A, Jones L, Erhorn A, Masic D, Bentley H . IGH@ translocations are prevalent in teenagers and young adults with acute lymphoblastic leukemia and are associated with a poor outcome. J Clin Oncol. 2014; 32(14):1453-62. DOI: 10.1200/JCO.2013.51.3242. View

15.

Fournier B, Balducci E, Duployez N, Clappier E, Cuccuini W, Arfeuille C . B-ALL With t(5;14)(q31;q32); Rearrangement and Eosinophilia: A Comprehensive Analysis of a Peculiar -Rearranged B-ALL. Front Oncol. 2020; 9:1374. PMC: 6914849. DOI: 10.3389/fonc.2019.01374. View

16.

Jung D, Giallourakis C, Mostoslavsky R, Alt F . Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol. 2006; 24:541-70. DOI: 10.1146/annurev.immunol.23.021704.115830. View

17.

Russell L, Capasso M, Vater I, Akasaka T, Bernard O, Calasanz M . Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood. 2009; 114(13):2688-98. DOI: 10.1182/blood-2009-03-208397. View

18.

Muppidi J, Schmitz R, Green J, Xiao W, Larsen A, Braun S . Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature. 2014; 516(7530):254-8. PMC: 4267955. DOI: 10.1038/nature13765. View

19.

Levin-Klein R, Bergman Y . Epigenetic regulation of monoallelic rearrangement (allelic exclusion) of antigen receptor genes. Front Immunol. 2014; 5:625. PMC: 4257082. DOI: 10.3389/fimmu.2014.00625. View