1. bookVolume 28 (2020): Issue 1 (January 2020)
Journal Details
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Journal
eISSN
2284-5623
First Published
08 Aug 2013
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4 times per year
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English
access type Open Access

A rare case of acute myeloid leukemia with ARHGEF12 (LARG, 11q23.3) and MAPRE1 (EB1, 20q11.21) fusion gene in an elderly patient

Published Online: 07 Feb 2020
Page range: 99 - 106
Received: 25 Dec 2019
Accepted: 11 Jan 2020
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
Abstract

Introduction. We report one elderly patient diagnosed with a rare subtype of acute myeloid leukemia (AML) and also with a very rare fusion gene involving ARHGEF12 (LARG, 11q23.3) and MAPRE1 (EB1, 20q11.21) genes.

Material and methods. Clinical examination and routine analysis were performed including peripheral blood smear, immunophenotyping of the peripheral blood by flow cytometry and several molecular analyses.

Results. Peripheral blood smear showed 80% blasts with round and some with convoluted nuclei, with basophilic cytoplasm, identified as monoblast and the majority of cells as promonocytes. Peripheral blood immunophenotyping was consistent with monocytic differentiation. Molecular analysis was negative for FLT3 ITD, FLT3 D835, NPM1, and DNMT3A R882 mutations. Multiplex ligation-dependent probe amplification revealed no copy number aberration. Ligation-dependent reverse transcription polymerase chain reaction (LD-RT-PCR) analysis identified the presence of one gene fusion between ARHGEF12 (LARG, 11q23.3) and MAPRE1 (EB1, 20q11.21) genes. The patient had no significant comorbidities, the renal function was normal and Eastern Cooperative Oncology Group performance status was 2 at diagnosis and 1 after treatment. She was treated with decitabine. She became transfusion independent and a reduction of the number of blasts was obtained.

Conclusions. The outcome of our AML patient was favorable but other patients with fusion genes involving ARHGEF12 (LARG, 11q23.3) and MAPRE1 (EB1, 20q11.21) should be reported, contributing to a better characterization of the disease, to monitor the minimal residual disease and in the end to more targeted treatment options. LD-RT-PCR represent a valuable multiplex technique for fusion gene analysis.

Keywords

1. Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7. DOI: 10.1016/j.lrr.2016.06.00110.1016/j.lrr.2016.06.001492765527408788Search in Google Scholar

2. Ofran Y, Tallman MS, Rowe J. How I treat acute myeloid leukemia presenting with preexisting comorbidities. Blood. 2016;128(4):488-96. DOI: 10.1182/blood-2016-01-63506010.1182/blood-2016-01-635060552453227235136Search in Google Scholar

3. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. DOI: 10.1182/blood-2016-03-64354410.1182/blood-2016-03-64354427069254Search in Google Scholar

4. Wang Y, Wu N, Liu D, Jin Y. Recurrent Fusion Genes in Leukemia: An Attractive Target for Diagnosis and Treatment. Curr Genomics. 2017;18(5):378-384. DOI: 10.2174/138920291866617032911034910.2174/1389202918666170329110349563564429081694Search in Google Scholar

5. Fu JF, Hsu HC, Shih LY. MLL is fused to EB1 (MAPRE1), which encodes a microtubule-associated protein, in a patient with acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2005;43(2):206-10. DOI: 10.1002/gcc.2017410.1002/gcc.2017415751040Search in Google Scholar

6. Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS et al. Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia. Proc Natl Acad Sci U S A. 2000;97(5):2145-50. DOI: 10.1073/pnas.04056919710.1073/pnas.0405691971576810681437Search in Google Scholar

7. Tripon F, Crauciuc GA, Moldovan VG, Bogliș A, Benedek IJ, Lázár E et al. Simultaneous FLT3, NPM1 and DNMT3A mutations in adult patients with acute myeloid leukemia - case study. Rev Romana Med Lab. 2019;27(3):245-54. DOI: 10.2478/rrlm-2019-002210.2478/rrlm-2019-0022Search in Google Scholar

8. Vázquez-Reyes A, Bobadilla-Morales L, Barba-Barba C, Macías-Salcedo G, Serafín-Saucedo G, Velázquez-Rivera ME et al. Aneuploidy identification in pre-B acute lymphoblastic leukemia patients at diagnosis by Multiplex Ligation-dependent Probe Amplification (MLPA). Leuk Res. 2017;59:117-123. DOI: 10.1016/j.leukres.2017.05.02210.1016/j.leukres.2017.05.02228624713Search in Google Scholar

9. Bănescu C. Do we really need genetic tests in current practice? Rev Romana Med Lab. 2019;27(1):9-14. DOI: 10.2478/rrlm-2019-001010.2478/rrlm-2019-0010Search in Google Scholar

10. Bănescu C, Tripon F, Trifa AP, Crauciuc AG, Bogliș A, Lazar E et al. Presence of copy number aberration and clinical prognostic factors in patients with acute myeloid leukemia: an analysis of effect modification. Pol Arch Intern Med. 2019;129(12):898-906. DOI: 10.20452/pamw.1509310.20452/pamw.1509331808755Search in Google Scholar

11. Ruminy P, Marchand V, Buchbinder N, Larson T, Joly B, Penther B et al. Multiplexed targeted sequencing of recurrent fusion genes in acute leukaemia. Leukemia. 2016;30(3):757-60. DOI: 10.1038/leu.2015.17710.1038/leu.2015.17726139430Search in Google Scholar

12. Verschuur A. Acute monocytic leukemia. Orphanet Encyclopedia 2004. Available at https://www.orpha.net/data/patho/GB/uk-AMLM5.pdf. (Last time accesed on 22 dec. 19)Search in Google Scholar

13. Bănescu C, Iancu M, Trifa AP, Cândea M, Benedek Lazar E, Moldovan VG et al. From Six Gene Polymorphisms of the Antioxidant System, Only GPX Pro198Leu and GSTP1 Ile105Val Modulate the Risk of Acute Myeloid Leukemia. Oxid Med Cell Longev. 2016;2016:2536705. DOI: 10.1155/2016/253670510.1155/2016/2536705470732526823947Search in Google Scholar

14. Arber DA, Brunning RD, Le Beau MM, Falini B, Vardiman JW, Porwit A et al. Acute myeloid leukemia with recurrent genetic abnormalities. In Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumors of haematopoietic and lymphoid tissues, Lyon: IARC. 2017, p 136-7.Search in Google Scholar

15. Borowitz MJ, Bene MC, Harris NL, Porwit A, Matutes E. Arber DA. Acute leukemias of ambiguous lineage. In Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumors of haematopoietic and lymphoid tissues, Lyon: IARC. 2017, p 183-4.Search in Google Scholar

16. DiNardo DC, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS et al. Venetoclax combined with decitabine or azacytidine in treatment naïve, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7-17. DOI: 10.1182/blood-2018-08-86875210.1182/blood-2018-08-868752631842930361262Search in Google Scholar

17. Chen Y, Kantarjian H, Pierce S, Faderl S, O’Brien S, Qiao W et al. Prognostic significance of 11q23 aberrations in adult acute myeloid leukemia and the role of allogeneis stem cell transplantation. Leukemia. 2013;27:836-42. DOI: 10.1038/leu.2012.31910.1038/leu.2012.319418153923135353Search in Google Scholar

18. Shih LY, Liang DC, Fu JF, Wu JH, Wang PN, Lin TL et al. Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement. Leukemia. 2006 Feb;20(2):218-23. DOI: 10.1038/sj.leu.240402410.1038/sj.leu.240402416341046Search in Google Scholar

19. Bogliş A, Tripon F, Bănescu C. The utility of molecular genetic techniques in craniosynostosis cases associated with intellectual disability. Rev Romana Med Lab. 2018;26(4):471-7. DOI: 10.2478/rrlm-2018-003310.2478/rrlm-2018-0033Search in Google Scholar

20. Crauciuc GA, Tripon F, Bogliş A, Făgărăşan A, Bănescu C. Multiplex ligation dependent probe amplification - A useful, fast and cost-effective method for identification of small supernumerary marker chromosome in children with developmental delay and congenital heart defect. Rev Romana Med Lab. 2018;26(4):461-70. DOI: 10.2478/rrlm-2018-003210.2478/rrlm-2018-0032Search in Google Scholar

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