Microgranular variant of acute promyelocytic leukemia with der(17) ins(17;15): A case report and review of the literature

Guan,Hongzai; Liu,Jing; Guo,Xiaofang; Wu,Chunmei; Yu,Huawei

doi:10.3892/etm.2015.2583

Microgranular variant of acute promyelocytic leukemia with der(17) ins(17;15): A case report and review of the literature

Authors:
- Hongzai Guan
- Jing Liu
- Xiaofang Guo
- Chunmei Wu
- Huawei Yu
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Affiliations: Department of Clinical Hematology, Medical College of Qingdao University, Qingdao, Shandong 266071, P.R. China, Clinical Laboratory of the Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Clinical Laboratory of No. 401 Hospital, PLA, Qingdao, Shandong 266071, P.R. China
Published online on: June 18, 2015 https://doi.org/10.3892/etm.2015.2583
Pages: 1009-1012

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Abstract

Acute promyelocytic leukemia (APL) with variant translocations is rare. The patient of the present case report, a 2‑year‑old male with a microgranular variant of APL carrying der(17) ins(17;15) translocation, exhibited fever and epistaxis. The complete blood count showed marked leukocytosis with 72% atypical promyelocytes, anemia and thrombocytopenia. Conventional cytogenetic analysis of the bone marrow cells revealed a karyotype of 47, XY, add(3)(q29), ‑7, ins(17;15)(q12;q14q22),+21,+mar. The promyelocytic leukemia/retinoic acid receptor α (PML/RARα) rearrangement and insertion were confirmed by fluorescence in situ hybridization. The PML/RARα transcripts were not detected by the reverse transcription polymerase chain reaction, and the patient was diagnosed with microgranular variant M3 APL. The patient achieved remission after a 30‑day treatment and was still in remission during a recent follow‑up. The present findings suggest that the ins(17;15) variant in APL may not be associated with an unfavorable prognosis. In summary, we reported an extremely rare case of APL with der(17) ins(17;15) abnormality in a pediatric patient and reviewed the literature.

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1	Diverio D, Lo Coco F, D'Adamo F, et al: Identification of DNA rearrangements at the retinoic acid receptor-alpha (RAR-alpha) locus in all patients with acute promyelocytic leukemia (APL) and mapping of APL breakpoints within the RAR-alpha second intron. Blood. 79:3331–3336. 1992.PubMed/NCBI
2	Yamanouchi J, Hato T, Niiya T, et al: A new four-way variant t(5;17;15;20)(q33;q12;q22;q11.2) in acute promyelocytic leukemia. Int J Hematol. 94:395–398. 2011. View Article : Google Scholar : PubMed/NCBI
3	Rowley JD, Golomb HM and Dougherty C: 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet. 1:549–550. 1977. View Article : Google Scholar : PubMed/NCBI
4	de Thé H, Chomienne C, Lanotte M, Degos L and Dejean A: The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature. 347:558–561. 1990. View Article : Google Scholar : PubMed/NCBI
5	Campbell LJ, Oei P, Brookwell R, et al: FISH detection of PML-RARA fusion in ins(15;17) acute promyelocytic leukemia depends on probe size. Biomed Res Int. 2013:1645012013. View Article : Google Scholar : PubMed/NCBI
6	Rizzatti EG, Portieres FL, Martins SL, Rego EM, Zago MA and Falcão RP: Microgranular and t(11;17)/PLZF-RARalpha variants of acute promyelocytic leukemia also present the flow cytometric pattern of CD13, CD34 and CD15 expression characteristic of PML-RARalpha gene rearrangement. Am J Hematol. 76:44–51. 2004. View Article : Google Scholar : PubMed/NCBI
7	Redner RL: Variations on a theme: The alternate translocations in APL. Leukemia. 16:1927–1932. 2002. View Article : Google Scholar : PubMed/NCBI
8	Zheng L, Xue Y, Li J, et al: Application of metaphase-fluorescence in situ hybridization to the diagnosis of acute promyelocytic leukemia and the detection of minimal residual disease. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 8:180–184. 2000.(In Chinese). PubMed/NCBI
9	Gallagher RE, Li YP, Rao S, et al: Characterization of acute promyelocytic leukemia cases with PML-RAR alpha break/fusion sites in PML exon 6: Identification of a subgroup with decreased in vitro responsiveness to all-trans retinoic acid. Blood. 86:1540–1547. 1995.PubMed/NCBI
10	Avvisati G, Lo Coco F and Mandelli F: Acute promyelocytic leukemia: Clinical and morphologic features and prognostic factors. Semin Hematol. 38:4–12. 2001. View Article : Google Scholar : PubMed/NCBI
11	Guglielmi C, Martelli MP, Diverio D, et al: Immunophenotype of adult and childhood acute promyelocytic leukaemia: Correlation with morphology, type of PML gene breakpoint and clinical outcome. A cooperative Italian study on 196 cases. Br J Haematol. 102:1035–1041. 1998. View Article : Google Scholar : PubMed/NCBI
12	Tallman MS, Kim HT, Montesinos P, et al: Does microgranular variant morphology of acute promyelocytic leukemia independently predict a less favorable outcome compared with classical M3 APL? A joint study of the North American Intergroup and the PETHEMA Group. Blood. 116:5650–5659. 2010. View Article : Google Scholar : PubMed/NCBI
13	Yoshii M, Ishida M, Yoshida T, et al: Clinicopathological features of acute promyelocytic leukemia: An experience in one institute emphasizing the morphological and immunophenotypic changes at the time of relapse. Int J Clin Exp Pathol. 6:2192–2198. 2013.PubMed/NCBI
14	Invernizzi R, Iannone AM, Bernuzzi S, et al: Acute promyelocytic leukemia: Morphological and clinical features. Haematologica. 78:156–161. 1993.PubMed/NCBI
15	Fang J, Chen SJ, Tong JH, Wang ZG, Chen GQ and Chen Z: Treatment of acute promyelocytic leukemia with ATRA and As₂ O₃: A model of molecular target-based cancer therapy. Cancer Biol Ther. 1:614–620. 2002. View Article : Google Scholar : PubMed/NCBI
16	Kim MJ, Cho SY, Lim G, et al: A rare case of microgranular acute promyelocytic leukemia associated with ider(17)(q10)t(15;17) in an old-age patient. Korean J Lab Med. 31:86–90. 2011. View Article : Google Scholar : PubMed/NCBI
17	Tang H, Liu ZF and Pan JL: The clinical and experimental research of 2 cases of acute promyelocytic leukemia with atypical t(15;17) translocation. Guo Ji Shu Xue Ji Xue Ye Xue Za Zhi. 35:315–317. 2012.(In Chinese).
18	Kurian S, Hogan TF, Bleigh OC, Dowdy YG, Merghoub T, Pandolfi PP and Wenger SL: Atypical t(15;17)(q13;q12) in a patient with all-trans retinoic acid refractory secondary acute promyelocytic leukemia: A case report and review of the literature. Cancer Genet Cytogenet. 138:143–148. 2002. View Article : Google Scholar : PubMed/NCBI
19	Chen SN, Xue YQ, Wu YF and Pan JL: Cytogenetic and molecular genetic studies on a variant of t(15;17), ins(17;15)(q21;q14q22), in an acute promyelocytic leukemia patient. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 21:77–79. 2004.(In Chinese). PubMed/NCBI
20	Grimwade D, Gorman P, Duprez E, et al: Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia. Blood. 90:4876–4885. 1997.PubMed/NCBI
21	Grimwade D, Biondi A, Mozziconacci MJ, 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
22	Haimi M, Elhasid R, Weyl Ben-Arush M, Brill-Zamir R, Laevski I and Gershoni-Baruch R: Derivative (7)t(7;8)(q34;q21): An additional chromosome aberration in acute promyelocytic leukemia-prognostic influence debated. Cancer Genet Cytogenet. 153:81–83. 2004. View Article : Google Scholar : PubMed/NCBI
23	Cervera J, Montesinos P, Hernández-Rivas JM, et al: Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Haematologica. 95:424–431. 2010. View Article : Google Scholar : PubMed/NCBI
24	Wan TS, Ma SK, Au WY, Liu HS, Chan JC and Chan LC: Trisomy 21 and other chromosomal abnormalities in acute promyelocytic leukemia. Cancer Genet Cytogenet. 140:170–173. 2003. View Article : Google Scholar : PubMed/NCBI
25	Bastos EF, Silva LA, Ramos MC, et al: Trisomy 11 as an additional chromosome alteration in a child with acute promyelocytic leukemia with poor prognosis. Case Rep Genet. 2012:6590162012.PubMed/NCBI
26	Xue Y, Lu D, Yuan YZ, Guo Y and Xie X: A rare variant translocation t(3;8)(q29;q22) without AML1/ETO fusion transcript in a case of oligoblastic leukemia. Leuk Res. 22:1015–1019. 1998. View Article : Google Scholar : PubMed/NCBI
27	Hasle H, Alonzo TA, Auvrignon A, et al: Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: An international retrospective study. Blood. 109:4641–4647. 2007. View Article : Google Scholar : PubMed/NCBI
28	Spell DW, Velagaleti GV, Jones DV and Velasquez WS: Translocation (15;17) and trisomy 21 in the microgranular variant of acute promyelocytic leukemia. Cancer Genet Cytogenet. 132:74–76. 2002. View Article : Google Scholar : PubMed/NCBI