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Kim, Park, Jang, Moon, and Kang: A Novel Four-Way Translocation t(5;9;22;18)(q31;q34;q11.2;q21) in a Patient with Chronic Myelogenous Leukemia
Original Article

Lab Med Online 2015;5(2):101-105.

Published online: 20 April 2015

DOI: https://doi.org/10.3343/lmo.2015.5.2.101

A Novel Four-Way Translocation t(5;9;22;18)(q31;q34;q11.2;q21) in a Patient with Chronic Myelogenous Leukemia

Woo-Seong Kim, M.D, Geon Park, M.D, Sook-Jin Jang, M.D, Dae-Soo Moon, M.D, Seong-Ho Kang, M.D

Department of Laboratory Medicine, Chosun University College of Medicine, Gwangju, Korea

Corresponding author: Seong-Ho Kang Department of Laboratory Medicine, Chosun University College of Medicine, 365 Pilmun-daero, Dong-gu, Gwangju 501-717, Korea Tel: +82-62-220-3254, Fax: +82-62-232-2063 E-mail: seonghomed@hanmail.net

Received 27 March 2014       Revised 20 August 2014       Accepted 24 September 2014

Copyright © 2015 The Korean Society for Laboratory Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chronic myelogenous leukemia (CML) is characterized by the presence of the Philadelphia chromosome, which is generated by a reciprocal t(9;22) (q34;q11) translocation. Variant Philadelphia chromosomes, found in 5–10% of CML cases, are a result of translocations involving other chromosomes, in addition to 9 and 22. These four-way Philadelphia chromosome translocations are very rare; only about 60 patients with such chromosomes have been described. Here, we report a CML case with a novel four-way variant Philadelphia chromosome. A conventional chromosome analysis of bone marrow cells revealed a 46, XY, t(5;9;22;18)(q31;q34;q11.2;q21) karyotype, which was confirmed by multicolor fluorescence in situ hybridization. The major BCR-ABL1 fusion gene was detected by reverse transcription-nested PCR. The patient was treated with imatinib. Twelve months after treatment, he demonstrated a complete hematologic response and chromosome analysis showed that he had a normal karyotype.

Keywords: Chronic myelogenous leukemia, Four-way Philadelphia translocation, Imatinib

References

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Fig. 1.
(A) G-banded karyotype of bone marrow cells demonstrating the t(5;9;22;18)(q31;q34;q11.2;q21) translocation. Arrows indicate rearranged chromosomes. (B) Gel electrophoresis of the reverse transcriptase-nested PCR products. It demonstrated the BCR-ABL1 gene rearrangement. Lane 1, molecular weight marker; Lane 2, a 443-bp band corresponding to the b3a2 rearrangement from the patient; Lane 3, positive control (b3a2, 443 bp); Lane 4, negative control.
lmo-5-101f1.tif
Fig. 2.
Karyotype of a bone marrow cell using multicolor fluorescence in situ hybridization. A four-way translocation involving chromosomes 5, 9, 18, and 22 was identified. Arrows indicate the four rearranged chromosomes.
lmo-5-101f2.tif
Table 1.
Patient characteristics and responses to imatinib of 15 chronic myelogenous leukemia patients with a 4-way translocation
Case No. Age/Sex Karyotype at diagnosis CML phase at diagnosis Mechanism Der(9) deletion Response to imatinib at 12 months
1 (Yin et al. 2004)[16] 54/F 46, XX, t(9;22;19;20)(q34;q11;p13.1;q22) CP NA No Imatinib failure
2 (Richebourg et al. 2008)[15] NA/M 46, XY, t(2;9;22;19)(q24;q34;q11;q14) CP 1-step No CCyR
3 (Richebourg et al. 2008)[15] NA/M 46, XY, t(4;9;22;21)(q12;q34;q11;q22) CP 1-step No CCyR
4 (Richebourg et al. 2008)[15] NA/F 46, XX, t(4;7;9;22)(q21;q15;q34;q11) CP 1-step No CCyR
5 (Richebourg et al. 2008)[15] NA/M 45, X, -Y, t(8;9;22;15)(q24;q34;q11;q25) CP 1-step Yes PCyR
6 (Richebourg et al. 2008)[15] NA/M 46, XY, t(9;22;12;13)(q34;q11;q11;q13) CP 2-step No CCyR
7 (Pienkowska-Grela et al. 2009)[17] NA/M 46, XY, t(3;9;22;12)(p21;q34;q11;q22) NA NA No PCyR or MiCyR or NR
8 (Kubota & Waki 2010)[18] 60/M 46, XY, t(6;13;9;22)(p21;q32;q34;q11) CP NA No CCyR (at 6 months)
9 (Stagno et al. 2010)[19] 44/M 46, XY, t(2;6;9;22) CP NA NA PCyR
10 (Okada et al. 2011)[10] 66/F 46, XX, t(9;22;15;19) (q34;q11;q15;q13) CP 1-step No Imatinib failure
11 (Marzocchi et al. 2011)[3] NA/M 46, XY, t(5;9;22;17)(q12;q34;q11;q11) CP 1-step No CCyR
12 (Marzocchi et al. 2011)[3] NA/M 46, XY, t(9;22;16;17)(q34;q11;?;?) CP NA No CCyR
13 (Adriana & Al Bahar 2012)[8] 64/M 46, XY, t(9;22;7;1)(q34;q11;q22;p13) CP 2-step No PCyR
14 (Koshiyama et al. 2013)[20] 29/M 46, XY, t(6;6;9;22)(q21;p21.3;q34;q11.2) CP NA NA CCyR
Present case 42/M 46, XY, t(5;9;22;18)(q31;q34;q11.2;q21) CP NA NA CCyR

Cytogenetic response (based on the conventional chromosome analysis, % Ph-positive cells): CCyR=0%, PCyR=1–35%, MiCyR >35%. Abbreviations: CML, chronic myelogenous leukemia; F, female; M, male; CP, chronic phase; CCyR, complete cytogenetic response; PCyR, partial cytogenetic response; MicyR, minor cytogenetic response; NR, no response; NA, not available.

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