PKMYT1 is a targetable vulnerability in del(17p) high-risk multiple myeloma.

PKMYT1 inhibition induces DNA damage and cell death specifically in del(17p) multiple myeloma cells, offering a targeted therapeutic approach.

• Why it matters: del(17p) is a highly adverse genetic abnormality in multiple myeloma, and current treatments lack specificity for this high-risk subgroup, necessitating new targeted strategies.
• What they did: Researchers integrated patient RNA sequencing and cell line dependency data to identify PKMYT1 as a vulnerability, then used genetic suppression and the inhibitor RP-6306 to test its effects in vitro and in vivo.
• The result: PKMYT1 inhibition caused DNA damage and cell death predominantly in del(17p) cells, reduced tumor burden, and extended survival in models, supporting its potential as a targeted therapy for high-risk MM.