A complex translocation (1;17;15) with spliced short‑type PML‑RARA fusion transcripts in acute promyelocytic leukemia: A case report

Lv,Lili; Yang,Longfei; Cui,Honghua; Ma,Tonghui

doi:10.3892/etm.2018.7091

A complex translocation (1;17;15) with spliced short‑type PML‑RARA fusion transcripts in acute promyelocytic leukemia: A case report

Authors:
- Lili Lv
- Longfei Yang
- Honghua Cui
- Tonghui Ma
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Affiliations: Department of Oncology and Hematology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
Published online on: December 13, 2018 https://doi.org/10.3892/etm.2018.7091
Pages: 1360-1366
Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The promyelocytic leukemia (PML)‑retinoic acid receptor α (RARA) fusion is hypothesized to serve a vital role in the pathogenesis of acute promyelocytic leukemia (APL), which results from a reciprocal translocation between chromosomes 15 and 17, t(15;17)(q24;q21). A minority of APL cases lack the classical t(15;17) and have been identified to have cryptic or masked t(15;17) or complex translocations. The present study reports on a case of a 37‑year‑old male with APL harboring a complex three‑way translocation t(1;17;15)(q21;q21;q24). This karyotypic interpretation was further confirmed by fluorescence in situ hybridization, and 98% of the bone marrow cells analyzed were positive for the PML‑RARA fusion gene. After combined treatment with all‑trans retinoic acid and arsenic trioxide, the patient achieved complete remission with no recurrence for 3 years to date. To the best of our knowledge, the present study is the first to report on the novel variant of t(15;17) involving the breakpoint 1q21.

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1	Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M and Vardiman JW: The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 127:2391–2405. 2016. View Article : Google Scholar : PubMed/NCBI
2	Grimwade D, Biondi A, Mozziconacci MJ, Hagemeijer A, Berger R, Neat M, Howe K, Dastugue N, Jansen J, Radford-Weiss I, et al: Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): Results of the european working party. Groupe français de cytogénétique hématologique, groupe de français d'hematologie cellulaire, UK cancer cytogenetics group and BIOMED 1 european community-concerted action ‘molecular cytogenetic diagnosis in haematological malignancies’. Blood. 96:1297–1308. 2000.PubMed/NCBI
3	Chen WX, Zhu HL, Xue M, Zhou H, Zhao F, Yan N and Chen Y: Quick staining technique for myeloperoxidase using potassium iodide and oxidized pyronine B. Acta Histochem. 116:292–296. 2014. View Article : Google Scholar : PubMed/NCBI
4	Gale RE, Hills R, Pizzey AR, Kottaridis PD, Swirsky D, Gilkes AF, Nugent E, Mills KI, Wheatley K, Solomon E, et al: Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia. Blood. 106:3768–3776. 2005. View Article : Google Scholar : PubMed/NCBI
5	Montesinos P and Sanz MA: The differentiation syndrome in patients with acute promyelocytic leukemia: Experience of the pethema group and review of the literature. Mediterr J Hematol Infect Dis. 3:e20110592011. View Article : Google Scholar : PubMed/NCBI
6	Wang Y, Ma J, Liu X, Liu R, Xu L, Wang L, Cen J and Chu X: A complex translocation (3;17;15) in acute promyelocytic leukemia confirmed by fluorescence in situ hybridization. Oncol Lett. 12:4717–4719. 2016. View Article : Google Scholar : PubMed/NCBI
7	Zhang R, Kim YM, Wang X, Li Y, Pang H, Lee JY and Li S: Coexistence of t(15;17) and t(15;16;17) detected by fluorescence in situ hybridization in a patient with acute promyelocytic leukemia: A case report and literature review. Oncol Lett. 8:1001–1008. 2014. View Article : Google Scholar : PubMed/NCBI
8	Bennour A, Tabka I, Youssef YB, Zaier M, Hizem S, Khelif A, Saad A and Sennana H: A PML/RARA chimeric gene on chromosome 12 in a patient with acute promyelocytic leukemia (M4) associated with a new variant translocation: t(12;15;17)(q24;q24;q11). Med Oncol. 30:4092013. View Article : Google Scholar : PubMed/NCBI
9	Osella P, Wyandt H, Vosburgh E and Milunsky A: Report of a variant t(1;15;17)(p36;q22;q21.1) in a patient with acute promyelocytic leukemia. Cancer Genet Cytogenet. 57:201–207. 1991. View Article : Google Scholar : PubMed/NCBI
10	Park JP and Fairweather RB: Complex t(1;15;17) in acute promyelocytic leukemia with duplication of RAR alpha and PML sequences. Cancer Genet Cytogenet. 89:52–56. 1996. View Article : Google Scholar : PubMed/NCBI
11	Galieni P, Marotta G, Vessichelli F, Diverio D, Minoletti F, Bucalossi A, Lo Coco F and Lauria F: Variant t(1;15;17)(q23;q22;q23) in a case of acute promyelocytic leukemia. Leukemia. 10:1658–1661. 1996.PubMed/NCBI
12	Miyazaki K, Kikukawa M, Kiuchi A, Shin K, Iwamoto T and Ohyashiki K: Complex translocations derived stepwise from standard t(15;17) in a patient with variant acute promyelocytic leukemia. Cancer Genet Cytogenet. 176:127–130. 2007. View Article : Google Scholar : PubMed/NCBI
13	Zhang Y and Rowley JD: Chromatin structural elements and chromosomal translocations in leukemia. DNA Repair (Amst). 5:1282–1297. 2006. View Article : Google Scholar : PubMed/NCBI
14	Tse W, Zhu W, Chen HS and Cohen A: A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells. Blood. 85:650–656. 1995.PubMed/NCBI
15	Busson-Le Coniat M, Salomon-Nguyen F, Hillion J, Bernard OA and Berger R: MLL-AF1q fusion resulting from t(1;11) in acute leukemia. Leukemia. 13:302–306. 1999. View Article : Google Scholar : PubMed/NCBI
16	Nguyen TT, Ma LN, Slovak ML, Bangs CD, Cherry AM and Arber DA: Identification of novel Runx1 (AML1) translocation partner genes SH3D19, YTHDf2, and ZNF687 in acute myeloid leukemia. Genes Chromosomes Cancer. 45:918–932. 2006. View Article : Google Scholar : PubMed/NCBI
17	Beitinjaneh A, Jang S, Roukoz H and Majhail NS: Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations in acute promyelocytic leukemia: A systematic review. Leuk Res. 34:831–836. 2010. View Article : Google Scholar : PubMed/NCBI
18	Souza Melo CP, Campos CB, Dutra ÁP, Neto JC, Fenelon AJ, Neto AH, Carbone EK, Pianovski MA, Ferreira AC and Assumpcão JG: Correlation between FLT3-ITD status and clinical, cellular and molecular profiles in promyelocytic acute leukemias. Leuk Res. 39:131–137. 2015. View Article : Google Scholar : PubMed/NCBI
19	Lucena-Araujo AR, Kim HT, Jacomo RH, Melo RA, Bittencourt R, Pasquini R, Pagnano K, Fagundes EM, Chauffaille Mde L, Chiattone CS, et al: Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: An International Consortium on Acute Promyelocytic Leukemia study. Ann Hematol. 93:2001–2010. 2014. View Article : Google Scholar : PubMed/NCBI
20	Poiré X, Moser BK, Gallagher RE, Laumann K, Bloomfield CD, Powell BL, Koval G, Gulati K, Holowka N, Larson RA, et al: Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): Prognostic significance of FLT3 mutations and complex karyotype. Leuk Lymphoma. 55:1523–1532. 2014. View Article : Google Scholar : PubMed/NCBI
21	Cicconi L, Divona M, Ciardi C, Ottone T, Ferrantini A, Lavorgna S, Alfonso V, Paoloni F, Piciocchi A, Avvisati G, et al: PML-RARα kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy. Leukemia. 30:1987–1992. 2016. View Article : Google Scholar : PubMed/NCBI
22	Wiernik PH, Sun Z, Gundacker H, Dewald G, Slovak ML, Paietta E, Kim HT, Appelbaum FR, Cassileth PA and Tallman MS: Prognostic implications of additional chromosome abnormalities among patients with de novo acute promyelocytic leukemia with t(15;17). Med Oncol. 29:2095–2101. 2012. View Article : Google Scholar : PubMed/NCBI
23	Fujishima M, Takahashi N, Miura I, Kobayashi Y, Kume M, Nishinari T and Miura AB: A PML/RARA chimeric gene on chromosome 2 in a patient with acute promyelocytic leukemia (M3) associated with a new variant translocation: t(2;15;17)(q21;q22;q21). Cancer Genet Cytogenet. 120:80–82. 2000. View Article : Google Scholar : PubMed/NCBI
24	Hernández JM, Martín G, Gutiérrez NC, Cervera J, Ferro MT, Calasanz MJ, Martínez-Climent JA, Luño E, Tormo M, Rayón C, et al: Additional cytogenetic changes do not influence the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with an ATRA plus anthracyclin based protocol. A report of the Spanish group PETHEMA. Haematologica. 86:807–813. 2001.PubMed/NCBI
25	De Botton S, Chevret S, Sanz M, Dombret H, Thomas X, Guerci A, Fey M, Rayon C, Huguet F, Sotto JJ, et al: Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL) do not confer poor prognosis: Results of APL 93 trial. Br J Haematol. 111:801–806. 2000. View Article : Google Scholar : PubMed/NCBI
26	de Botton S, Coiteux V, Chevret S, Rayon C, Vilmer E, Sanz M, de La Serna J, Philippe N, Baruchel A, Leverger G, et al: Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. J Clin Oncol. 22:1404–1412. 2004. View Article : Google Scholar : PubMed/NCBI
27	Freeman CE, Mercer DD, Ye Y, Van Brunt J III and Li MM: Cytogenetic and molecular characterization of complex three-way translocations in acute promyelocytic leukemia. Beijing Da Xue Xue Bao Yi Xue Ban. 41:477–479. 2009.PubMed/NCBI
28	McKinney CD, Golden WL, Gemma NW, Swerdlow SH and Williams ME: RARA and PML gene rearrangements in acute promyelocytic leukemia with complex translocations and atypical features. Genes Chromosomes Cancer. 9:49–56. 1994. View Article : Google Scholar : PubMed/NCBI
29	Calabrese G, Min T, Stuppia L, Powles R, Swansbury JG, Morizio E, Peila R, Donti E, Fioritoni G and Palka G: Complex chromosome translocations of standard t(8;21) and t(15;17) arise from a two-step mechanism as evidenced by fluorescence in situ hybridization analysis. Cancer Genet Cytogenet. 91:40–45. 1996. View Article : Google Scholar : PubMed/NCBI