Network Analysis Reveals Synergistic Genetic Dependencies for Rational Combination Therapy in Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia.

ABSTRACT:

Purpose

Systems biology approaches can identify critical targets in complex cancer signaling networks to inform new therapy combinations that may overcome conventional treatment resistance.

Experimental design

We performed integrated analysis of 1,046 childhood B-ALL cases and developed a data-driven network controllability-based approach to identify synergistic key regulator targets in Philadelphia chromosome-like B-acute lymphoblastic leukemia (Ph-like B-ALL), a common high-risk leukemia subtype associated with hyperactive signal transduction and chemoresistance.

Results

We identified 14 dysregulated network nodes in Ph-like ALL involved in aberrant JAK/STAT, Ras/MAPK, and apoptosis pathways and other critical processes. Genetic cotargeting of the synergistic key re

SUBMITTER: Ding YY 

PROVIDER: S-EPMC8448976 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature