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.
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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](/upload/SynapseXML/0192lmo/thumb/lmo-5-101f1.gif)
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](/upload/SynapseXML/0192lmo/thumb/lmo-5-101f2.gif)
Table 1.
Patient characteristics and responses to imatinib of 15 chronic myelogenous leukemia patients with a 4-way translocation
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.