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Updated: Aug 16, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

TP53 mutation drives unique transcriptional and functional vulnerabilities independent of del(17p) in multiple

Dimitrios Tsallos1, Nemo Ikonen1, Juho J Miettinen1

  • 1Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland.

Iscience
|August 15, 2026
PubMed

Insights

TP53 mutations in multiple myeloma (MM) create vulnerabilities in cell division and metabolism, increasing sensitivity to certain therapies. Understanding these TP53-associated weaknesses can help optimize treatments for high-risk MM patients.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • TP53 abnormalities are linked to treatment resistance and poor prognosis in multiple myeloma (MM).
  • The functional consequences of TP53 alterations in MM remain incompletely understood.
  • Targeting TP53-associated vulnerabilities could improve therapeutic strategies.

Purpose of the Study:

  • To characterize TP53-associated vulnerabilities in multiple myeloma.
  • To identify specific drug sensitivities in TP53-mutated MM.
  • To refine TP53 classification for optimizing high-risk MM treatment.

Main Methods:

  • Integrated analysis of ex vivo drug sensitivity profiling, genomics, transcriptomics, and proteomics.
  • Utilized genome-wide CRISPR-Cas9 and RNAi screening in 167 CD138+ bone marrow patient samples.
  • Compared drug response profiles across TP53-mutated, del(17p), and wild-type TP53 MM.

Main Results:

  • TP53-mutated MM shows dependencies on spindle organization, mitotic regulation, DNA synthesis, and transcriptional/metabolic pathways.
  • TP53-mutated MM cells are more sensitive to chemotherapeutics, HDAC, HSP90, IGF1R, PI3K/AKT/mTOR inhibitors, and plicamycin.
  • Distinct drug response profiles were observed for MM with del(17p) and wild-type TP53.

Conclusions:

  • TP53 mutations confer specific vulnerabilities in multiple myeloma.
  • Identifying these vulnerabilities allows for tailored therapeutic approaches.
  • Refined TP53 classification can optimize treatment strategies for high-risk MM.
Keywords:
del(17p)drug sensitivityhigh-risk genetic abnormalitiesmulti-omic profilingmultiple myelomaprecision oncologytherapeutic vulnerabilitiestp53 mutation

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