Bortezomib induced peripheral neuropathy and single nucleotide polymorphisms in PKNOX1

Xiang Zhou; Seungbin Han; Nadine Cebulla; Larissa Haertle; Maximilian J Steinhardt; Daniel Schirmer; Eva Runau; Leon Flamm; Calvin Terhorst; Laura Jähnel; Cornelia Vogt; Silvia Nerreter; Eva Teufel; Emilia Stanojkovska; Julia Mersi; Umair Munawar; Magnus Schindehütte; Robert Blum; Ann-Kristin Reinhold; Oliver Scherf-Clavel; Heike L Rittner; Mirko Pham; Leo Rasche; Hermann Einsele; Claudia Sommer; K Martin Kortüm

doi:10.1186/s40364-023-00490-9

Bortezomib induced peripheral neuropathy and single nucleotide polymorphisms in PKNOX1

Biomark Res. 2023 May 16;11(1):52. doi: 10.1186/s40364-023-00490-9.

Authors

Xiang Zhou^#¹, Seungbin Han^#¹, Nadine Cebulla², Larissa Haertle^{1

3}, Maximilian J Steinhardt¹, Daniel Schirmer², Eva Runau², Leon Flamm², Calvin Terhorst², Laura Jähnel², Cornelia Vogt¹, Silvia Nerreter¹, Eva Teufel¹, Emilia Stanojkovska¹, Julia Mersi¹, Umair Munawar¹, Magnus Schindehütte⁴, Robert Blum², Ann-Kristin Reinhold⁵, Oliver Scherf-Clavel⁶, Heike L Rittner⁵, Mirko Pham⁴, Leo Rasche¹, Hermann Einsele¹, Claudia Sommer², K Martin Kortüm⁷

Affiliations

¹ Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.
² Department of Neurology, University Hospital of Würzburg, Würzburg, Germany.
³ Department of Hematology, Spanish National Cancer Research Center (CNIO), Hospital Universitario 12 de Octubre, Complutense University Madrid, Madrid, Spain.
⁴ Department of Neuroradiology, University Hospital of Würzburg, Würzburg, Germany.
⁵ Center for Interdisciplinary Medicine, Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital of Würzburg, Würzburg, Germany.
⁶ Department of Clinical Pharmacy, University of Würzburg, Würzburg, Germany.
⁷ Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany. [email protected].

^# Contributed equally.

Abstract

We analyzed single nucleotide polymorphisms (SNPs) in PKNOX1 (rs2839629) and in the intergenic region between PKNOX1 and CBS (rs915854) by Sanger sequencing in 88 patients with multiple myeloma treated with bortezomib. All patients (n = 13) harboring a homozygous mutation in PKNOX1 (rs2839629) also had a homozygous mutated rs915854 genotype. Homozygous mutated genotypes of rs2839629 and rs915854 were significantly enriched in patients with painful peripheral neuropathy (PNP) (P < 0.0001), and homozygous mutated rs2839629 genotype was significantly enriched in patients with pain compared to patients with no pain (P = 0.04). In summary, both SNPs rs2839629 and/or rs915854 may be potential biomarkers predicting an increased risk to develop painful PNP under bortezomib.

Keywords: Bortezomib; Multiple myeloma; PKNOX1; Peripheral neuropathy.

Publication types

Letter