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. 2019 Feb 15:11:1559-1567.
doi: 10.2147/CMAR.S189025. eCollection 2019.

Identification of chromosomal abnormalities and genomic features in near-triploidy/tetraploidy-acute leukemia by fluorescence in situ hybridization

Ruqing Yang  1 , Minghua Jiang  2 , Junzhao Zhao  1 , Hui Chen  2 , Jian Gong  2 , Yaying You  3 , Laiyue Song  3 , Zhen Li  4 , Qian Li  2
Affiliations

Identification of chromosomal abnormalities and genomic features in near-triploidy/tetraploidy-acute leukemia by fluorescence in situ hybridization

Ruqing Yang et al. Cancer Manag Res. .

Abstract

Background: Near-triploidy/tetraploidy is rarely found in acute leukemia. Only limited data are available to characterize this condition, and it remains largely unknown.

Patients and methods: In our study, we performed karyotype analysis on 1,031 patients diagnosed with acute leukemia from 2006 to 2018. A total of 10 patients of near-triploidy/tetraploidy karyotype were enrolled. Two cases of near-triploidy (66-79 chromosomes) and eight cases of near-tetraploidy (84-100 chromosomes) were identified. Bone marrow samples of these 10 patients were analyzed by fluorescence in situ hybridization with 19 commercially available probes that detected a small portion of gene alterations and large regions of chromosome amplifications.

Results: Of the six patients with acute myelocytic leukemia, we detected three cases of double t(8;21)(q22;q22) that have not been previously reported, and one of them demonstrated ins(21;8) (q22;q24q22). We also describe a novel pediatric case carrying double t(15;17)(q22;q21) and receiving targeted treatment with all-trans retinoic acid therapy. To date, this case has responded well to the regimen and has shown continuous complete remission. All patients received chemotherapy. One of them received allogeneic hematopoietic stem cell transplant (HSCT) and survived for 22 months. Eight of the 10 patients died, and the median overall survival was 11 months.

Conclusion: Using fluorescence in situ hybridization, we identified the distinct complex karyotype of near-triploidy/tetraploidy and provided further prognostic information. Tetraploidy acute promyelocytic leukemia had favorable prognosis; thus, HSCT was not necessary. The case of insertion t(21;8)(q22;q24q22) in tetraploidy responded poorly to chemotherapy and achieved molecular remission with difficultly. Data from patients in this group indicated that near-triploidy/tetraploidy acute leukemia has poor prognosis and new therapy is urgently needed.

Keywords: acute leukemia; fluorescence in situ hybridization; gene; near-triploidy; tetraploidy karyotype.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
BM morphologic features. Notes: (A-1) (Case 7): Blasts are large with multiple and irregular nuclei and large nucleoli; cytoplasm is dark blue and filled with granules and prominent cytoplasmic vacuoles (arrow). Peripheral blood (A-2) (Case 7): Auer rod (arrow). (B) (Case 9): Blasts are different in size with pleomorphic nuclei and prominent nucleoli. Multinucleate blasts (arrow). (C) (Case 10): Blasts are different in size and filled with granules and prominent cytoplasmic pseudopodia. Faggot cell (arrow). (D) (Case 3): Atypical large blasts with irregular nuclear outlines and frequent cytoplasmic vacuoles, showing large nuclei and nucleoli. (E) (Case 2): Blasts are large with prominent, multiple, and pleomorphic nuclei. Magnification ×1000. Abbreviation: BM, bone marrow.
Figure 2
Figure 2
Karyotype and FISH analysis (Case 7). Notes: Numbers 1–22 represent chromosomes. (A) Karyotype of diploidy (R-banding): 46, XY, t (8;21)(q22;q22). 8q-(red arrow) and 21q+ (green arrow). (B) Karyotype of tetraploidy (R-banding): 92, XXYY, t(8;21)(q22;q22)×2. 8q-(red arrow) and 21q+ (green arrow). (C) FISH analysis with GLP RUNX1–RUNX1T1 dual color fusion probe (located at 21q22/8q22). Revealing 2F4O4G signals. Two fusions on the end of 21q+, four red signals (red arrow) are on native chromosome 8 and 8q−, two green signals proximal to the centromere of 21q+ (yellow arrow), and two native chromosome 21 (green arrow). (D) FISH analysis with GLP C-MYC dual color break-apart probe (located at 8q24); the picture displays that 8q24 (MYC) (red arrow) had not moved to 21q+. (E) FISH analysis with GLP ETV6–RUNX1 dual color fusion probe (located at 12p13/21q22). Tetraploidy metaphase shows red signals (red arrow) on chromosome 12, and six green signals (green arrow) consist of two on native chromosome 21 and four on 21q+×2. Magnification ×1000. Abbreviation: FISH, fluorescence in situ hybridization.
Figure 3
Figure 3
Karyotype and FISH analysis (Case 9). Notes: Numbers 1 -22 represent chromosomes. (A) Karyotype (R-banding): 86, XXYY, −5, –5, –7, I (11q)×2, –13, −13, –18. Red arrow represents isodicentric 11q chromosomes. (B) FISH analysis with GLP MLL dual color break-apart probe (located at 11q23). The probe confirms two idic (11q) chromosomes (red arrow). Magnification ×1000. Abbreviation: FISH, fluorescence in situ hybridization.
Figure 4
Figure 4
Genes change in near-triploid/tetraploid-AL in 10 cases. Abbreviation: AL, acute leukemia.
See this image and copyright information in PMC

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