title: Measurement of Proteasome Activity in Peripheral Blood Mononuclear Cells as an Indicator of Susceptibility to Bortezomib-Induced Severe Neurological Adverse Events in Patients with Multiple Myeloma.
abstract: OBJECTIVE
  To explore the biomarker for predicting the occurrence of adverse events in myeloma patients treated by intravenous bortezomib, we measured proteasome activity in peripheral blood mononuclear cells.
  
  
  METHODS
  Samples were obtained from 34 bortezomib-naïve patients. Proteasome activity was measured at pre- and postchemotherapy phase by using a synthetic substrate.
  
  
  RESULTS
  Bortezomib injection resulted in a dramatic decrease in proteasome activity, reaching 32.4 ± 18.79% (mean ± SD) of the pretreatment level at 1 h, but it generally recovered at the end of the first course. In total, 6 patients manifested with severe bortezomib-induced peripheral neuropathy (sBIPN) in the second-third course. There was a nonsignificant trend for these patients to have lower levels of the relative proteasome activity at the end of the first course than those without sBIPN (median: 74.03 vs. 103.2%, p = 0.052). Moreover, in all of them, proteasome activity did not recover to the pretreatment level, whereas no patients with complete recovery manifested with sBIPN. Analysis with Fisher's exact test demonstrated that incomplete recovery of proteasome activity is a significant risk factor for sBIPN (p = 0.014).
  
  
  CONCLUSIONS
  Patients with incomplete recovery of proteasome activity are at high risk for developing sBIPN, and the susceptible patients can be indicated by monitoring proteasome activity.
authors: Department of Medical Oncology, Ibaraki Prefectural Central Hospital, Kasama, Japan.
authors: Yukiko
authors: Y
authors: Cho
authors: Mitsuo
authors: M
authors: Hori
authors: Yasushi
authors: Y
authors: Okoshi
authors: Fumie
authors: F
authors: Fujisawa
authors: Atsushi
authors: A
authors: Shinagawa
authors: Daisuke
authors: D
authors: Kudo
authors: Takuya
authors: T
authors: Komeno
authors: Chikashi
authors: C
authors: Yoshida
authors: Yukitaka
authors: Y
authors: Katsura
authors: Ikuyo
authors: I
authors: Ota
authors: Seiichi
authors: S
authors: Shimizu
authors: Masaharu
authors: M
authors: Kamoshita
authors: Katsuhiro
authors: K
authors: Sasaki
authors: Keiji
authors: K
authors: Tanaka
authors: Harumi Y
authors: HY
authors: Mukai
authors: Hiroshi
authors: H
authors: Kojima
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D000069286:Bortezomib; D004198:Disease Susceptibility; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009363:Neoplasm Proteins; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex