A Case of Chronic Myeloid Leukemia With Rare Variant ETV6/ABL1 Rearrangement

Dear Editor, The translocation (9;12)(q34;p13) ETV6/ABL1 rearrangement is a rare but recurrent chromosomal translocation associated with a variety of hematological malignancies, including CML, atypical CML, AML, and ALL [1]. The structure of the ETV6/ABL1 oncoprotein is similar to that of BCR/ABL1, and they initiate similar downstream pathways [2]. There are two ETV6/ABL1 fusion isoforms: the type A isoform, which fuses ETV6 exon 4 with ABL1 exon 2; and the type B isoform, which fuses ETV6 exon 5 with ABL1 exon 2 [3, 4]. To date, 30 cases of ETV6/ABL1 fusion have been reported [5, 6], and only one of these cases resulted in CML with positive BCR/ABL1 rearrangement [7]. Herein, we report a rare case of CML with ETV6/ABL1 rearrangement. A 54-yr-old male was admitted with persistent leukocytosis. Complete blood counts showed a white blood cell count of 21.7 ×10/L with 1% blasts, Hb of 126 g/L, and platelet count of 294 ×10/L. Physical examination was unremarkable. Bone marrow (BM) analysis showed typical characteristics of CML (Fig. 1A, B). Chromosomal analysis of the BM cells demonstrated a balanced t(9;12)(q34;p13) translocation, which was not the Philadelphia chromosome (Fig. 1C). FISH analysis with probes for BCR/ABL1 (Abbott Vysis, Des Plaines, IL, USA detected no fusion signal. However, reverse transcriptase (RT)-PCR analysis of the BCR/ ABL1 fusion transcripts yielded positive results; the reaction product was 700 bp long, indicating positive rearrangement and hence, presence of the P230 chimeric protein at the molecular level (Fig. 1D). To visualize the ETV6/ABL1 fusion signal, we prepared a mixture of two commercially available, locus-specific identifiers: a BCR/ABL1 dual color, dual fusion translocation probe, and an ETV6/RUNX1 extra signal dual color translocation probe (Abbott Vysis) (Fig. 1E, F). Metaphase and interphase FISH with the mixed BCR/ABL1 and ETV6/RUNX1 probes showed one yellow fusion signal at 9q34, which was derived from a green signal from ETV6 and a red signal from ABL1 (Fig. 1G, H). RT-PCR analysis of the ETV6/ABL1 fusion transcript was positive for the 1,141-bp product, indicating a type B fusion (Fig. 1D). After diagnosis, the patient was transferred to another hospital, and therefore, follow-up BM examination was not possible. ETV6/ABL1 rearrangement has been reported to result in enhanced tyrosine kinase activity and neoplastic transformation [3, 8]. A total of 13 cases of ETV6/ABL1-positive or atypical CML have been reported to date (Table 1) [5, 7]. Among those cases, including the present case, two were BCR/ABL1 fusion-positive and 11 were either unknown or negative for the BCR/ABL1 fusion. Both BCR/ABL1 fusion-positive cases presented with per-