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

  • Rikio SuzukiEmail author
  • Takayuki Warita
  • Yoshihiko Nakamura
  • Yuka Kitamura
  • Yasuyuki Aoyama
  • Yoshiaki Ogawa
  • Hiroshi Kawada
  • Kiyoshi AndoEmail author
Case Report


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.


Multiple myeloma Double refractory Congenital abnormality t(4;14) t(11;22) 


Author 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.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.


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Copyright information

© Japanese Society of Hematology 2019

Authors and Affiliations

  1. 1.Department of Hematology/OncologyTokai University School of MedicineIseharaJapan
  2. 2.Center for Regenerative MedicineTokai University School of MedicineIseharaJapan

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