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ABL gene fuses BCR during t(20;22) results in Philadelphia-negative, but BCR/ABL-positive chronic myeloid leukemia

Leukemia volume 16, pages 951–952 (2002)Cite this article

Chronic myelogenous leukemia (CML) is usually characterized by the presence of the Philadelphia (Ph) translocation, t(9;22)(q34;q11). BCR-ABL fusion in Ph translocation is well known to be critical in the pathogenesis. The interest in treating this disease is now focused on a novel oncoprotein p210BCR-ABL as a target molecule. On the other hand, a minority of patients with CML have cytogenetically normal leukemic cells. A subgroup in Ph-negative patients showed a rearrangement of the major BCR.1 A previous report, analyzing patients with Ph-negative CML showed M-BCR rearrangement in 11 out of 23 patients.2 Insertion of a small segment of chromo- some 9 (9q34) into chromosome 22q11 was suggested to form M-BCR in Ph-negative CML.3,4 A unique complex translocation: t(9;12;15)(q34;q12;q21) in a CML patient has been reported to mask the Ph chromosome.5 Fluorescence in situ hybridization (FISH) has become useful to confirm cytogenetic diagnosis in Ph-positive and -negative CML.6 Seong et al,7 using hypermetaphase FISH, reported that two out of six Ph-negative CML patients had ABL insertions into the BCR gene on chromosome 22. In Ph-negative CML, retranslocation between chromosomes 9q+ and 22q− was postulated to result in normal-looking chromosomes 9 and 22.1 We here report a patient with t(20;22)(q13;q11) accompanying BCR-ABL fusion on chromosome 22 which resulted in a normal-looking cytogenetic study by the Giemsa-banding method.

Ph-negative and BCR-positive CML patients are now easily analyzed using molecular techniques. The finding of BCR-ABL molecular rearrangements indicates undetected Ph translocation in Ph-negative patients. Cytogenetic study in this patient failed to demonstrate Ph translocation. RT-PCR analysis indicated that this patient had BCR-ABL rearrangement. This finding was confirmed by dual-color FISH analysis demonstrating a BCR-ABL fusion signal on one chromosome 22. Meanwhile, karyotyping by SKY analysis demonstrated t(20;22) without abnormality in chromosome 9. These results indicate that only a small segment of chromosome 9 including ABL is located on chromosome 22. Inazawa et al1 speculated that retranslocation between chromosome 9 and 22 might result in Ph-negative CML. Other reports suggested insertion of a small segment of chromosome 9 into chromosome 22 to form M-BCR in Ph-negative CML.3,4 Moreover, masked Ph chromosomes in the literature usually have a 9q+ anomaly that inspires further examination of the translocated part on 9q34. However, the current case showed neither 9q+ nor 22q− anomaly using standard G- and Q-bandings.

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Acknowledgements

The authors are indebted to Professor J Patrick Barron of the International Medical Communications Center of Tokyo Medical University for his review of this manuscript.

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  1. First Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan

    Y Ito, T Shimamoto, Y Kuriyama, A Nakajima, M Sumi & K Ohyashiki

  2. Center for Molecular Biology and Cytogenetics, SRL Inc., Hino, Japan

    Y Watanabe, H Beppu & K Ohtsubo

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Ito, Y., Shimamoto, T., Kuriyama, Y. et al. ABL gene fuses BCR during t(20;22) results in Philadelphia-negative, but BCR/ABL-positive chronic myeloid leukemia. Leukemia 16, 951–952 (2002). https://doi.org/10.1038/sj.leu.2402441

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