Near-tetraploidy clone can evolve from a hyperdiploidy clone and cause resistance to lenalidomide and bortezomib in a multiple myeloma patient.
Aneuploidy is a very common prognostic factor in multiple myeloma (MM). Nonhyperdiploidy including near-tetraploidy (NT) is a poor prognostic indicator, compared to hyperdiploidy in multiple myeloma (MM). NT results from endoduplication of hypodiploidy. We report of a 55-year-old female patient diagnosed with advanced stage MM with hyperdiploidy and t(8;14)(q24;q32). The patient responded well to lenalidomide and dexamethasone for approximately 1 year. At the time of progression, she had become unresponsive to lenalidomide and subsequently bortezomib, and was found to have NT and loss of choromosome 13. There is another reported patient who had a possible interchange from nonhyperdiploidy to hyperdiploidy status, however, artifact could not be ruled out. To our knowledge, this is the first patient in whom evolution of an abnormal clone from a hyperdiploidy to a NT abnormal clone has been confirmed during the natural course of MM. This evolution is associated with resistance to novel drugs and poor prognosis in MM.
Department of Pathology, Medical College of Georgia, Augusta, GA 30912, USA.
Ji
J
Yuan
Radhika
R
Shah
Anita
A
Kulharya
Celalettin
C
Ustun
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000069286:Bortezomib; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D002883:Chromosomes, Human, Pair 14 / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure; D002999:Clone Cells / Q000187:drug effects / Q000648:ultrastructure; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007621:Karyotyping; D000077269:Lenalidomide; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000648:ultrastructure; D036102:Peripheral Blood Stem Cell Transplantation; D011123:Polyploidy; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014178:Translocation, Genetic; D014182:Transplantation, Autologous
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide