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A case of double-refractory multiple myeloma with both the IgH-MMSET fusion protein and the congenital abnormality t(11;22)

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Abstract

A 67-year-old female was referred to our hospital with a sternal fracture in March 2008. She received a diagnosis of multiple myeloma (MM) BJP-κ type (ISS stage III). G-banding karyotype revealed 46, XX, t(11;22)(q23.3;q11.2) (Hubacek, Gene 592:193–9, 2016), which was later confirmed to be congenital. After repeated rounds of chemotherapy with bortezomib and lenalidomide, she obtained a very good partial response in August 2014, and she was followed up with no treatment. However, she relapsed in February 2016. At that time, fluorescence in situ hybridization identified del(13q) and t(4;14)(p16;q32), which are associated with a poor prognosis. Furthermore, PCR analysis showed that the chromosome 11 breakpoint was at the APOA5/APOA4 locus at 11q23.3, which is associated with malignancy, and that the chromosome 22 breakpoint was at the SEPT5 intron 1 locus, which also plays a role in leukemogenesis through formation of a fusion gene with MLL. Although she was treated with three further lines of therapy, she died from disease progression in August 2017. Synergism between t(11;22) and t(4;14) may have induced the double-refractory phenotype to proteasome inhibitor and lenalidomide, at least during the chemorefractory phase. We present a biological analysis of this case and a review of the literature.

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Authors and Affiliations

  1. Department of Hematology/Oncology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, Japan

    Rikio Suzuki, Yasuyuki Aoyama, Yoshiaki Ogawa, Hiroshi Kawada & Kiyoshi Ando

  2. Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan

    Takayuki Warita, Yoshihiko Nakamura, Yuka Kitamura & Kiyoshi Ando

Authors
  1. Rikio Suzuki
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  2. Takayuki Warita
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  3. Yoshihiko Nakamura
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  4. Yuka Kitamura
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  5. Yasuyuki Aoyama
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  6. Yoshiaki Ogawa
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  7. Hiroshi Kawada
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  8. Kiyoshi Ando
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Contributions

R.S. and K.A. analyzed the clinical status of the patient, analyzed the data, and prepared the manuscript. T.W., Y.N., Y.K., Y.A., Y.O., and H.K. analyzed the data.

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Correspondence to Rikio Suzuki or Kiyoshi Ando.

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The authors declare no competing financial interests.

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Suzuki, R., Warita, T., Nakamura, Y. et al. A case of double-refractory multiple myeloma with both the IgH-MMSET fusion protein and the congenital abnormality t(11;22). Int J Hematol 109, 731–736 (2019). https://doi.org/10.1007/s12185-019-02603-3

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  • DOI: https://doi.org/10.1007/s12185-019-02603-3

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