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A case of therapy-related acute myeloid leukemia associated with inv(16), with subsequent development of t(9;22)

Leukemia volume 20, pages 746–748 (2006)Cite this article

The balanced chromosome aberrations, inv(16)(p13q22), is found in approximately 10–12% of de novo acute myeloid leukemia (AML) cases and is closely associated with the FAB subtype M4eo. Inv(16) results in the fusion of the CBFB gene at 16q22 to the smooth muscle myosin heavy chain (MYH11) gene at 16p13. Clinical studies have shown that patients with de novo AML with inv(16) achieve higher rates of complete remission (CR), and continuous CR when treated with high-dose cytarabine during the consolidation phase.1 The inv(16) is otherwise rarely reported in therapy-related AML (t-AML) patients. It was observed in breast cancer or lymphoma patients treated with alkylating agents, topoisomerase II inhibitors and/or radiation therapy. The additional cytogenetic abnormalities, combined with inv(16), observed in 54% of patients, were a large predominance of trisomy 8, 21 and 22 and deletion of 7q, or trisomy 13.2 But, there was no t-AML coexistence with inv(16) and t(9;22). Herein, a case of t-AML with inv(16), with the subsequent development of the t(9;22) abnormality, is reported.

The co-association of the inv(16) and the t(9;22) in patients with AML has only been reported in nine patients (Table 1).3, 4, 5 All 9 patients presented with the M4eo FAB subtype, with the exception of one, who presented with the AML M1 phenotype.6 Only p190BCR-ABL rearrangement was detected by molecular assessment. All were de novo AML, and to our knowledge, no case related to previous treatment has been reported. Our patient showed pancytopenia 10 months after the start of chemotherapy, which contained the topoisomerase II inhibitor, mitoxantrone. Although topoisomerase II inhibitor relates to the direct presentation of an overt leukemic state without a proceeding myelodysplastic syndrome (MDS) phase,1 this case unusually had a preleukemic phase showing a hypocellular marrow, with 10% blasts and 40% eosinophils. The bone marrow finings was mimicking the marrow relapse of primary lymphoma, because eosinophil infiltration is also commonly found in lymphoma cases. But, the cytogenetic results of 46,XX,inv(16)(p13.1q22) supported that the marrow was in a hypocellular preleukemic phase, which would be expected to progress to AML with inv(16). Just 1 month later, the marrow revealed M4eo findings, as expected. Moreover, two additional chromosomal changes were detected at this point of time, including trisomy 8/8q and variant type of t(9;22). Trisomy 8 is a well known secondary chromosomal abnormality in de novo AML and t-AML, but the late appearance of the t(9;22) is an unusual event in both conditions. The t(9;22)(q34;q11) represents 2% of all therapy-related MDS and t-AML. The t(9;22) was found to be significantly associated with previous therapy with topoisomerase II inhibitors.7 The latency period of this case was short, 10 months, and rapid clonal changes developed 1 month later. The t(9;22), associated with the p190BCR-ABL rearrangement, in this patient was a late appearing, therapy-related clonal evolution. The previously reported cases co-associated with the inv(16) and t(9;22) suggested that the t(9;22) could be a secondary event.4, 5 Our case provides the definite evidence of this suggestion by serial cytogenetic and morphologic evaluation at an interval of 1 month.

Table 1 Previously reported cases coexistence with inv(16) and t(9;22) in AML
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  1. Department of Clinical Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea

    M Kim, J Lim, Y Kim, K Han & C-S Kang

  2. Division of Hematology, Department of Internal-Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

    H-J Kim & W-S Min

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Kim, M., Lim, J., Kim, Y. et al. A case of therapy-related acute myeloid leukemia associated with inv(16), with subsequent development of t(9;22). Leukemia 20, 746–748 (2006). https://doi.org/10.1038/sj.leu.2404058

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