Notch1 gene mutations target KRAS G12D-expressing CD8+ cells and contribute to their leukemogenic transformation

Guangyao Kong, Juan Du, Yangang Liu, Benjamin Meline, Yuan I. Chang, Erik A. Ranheim, Jinyong Wang, Jing Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Background: Endogenous oncogenic Kras induces a highly penetrant acute T-cell lymphoblastic leukemia/lymphoma (T-ALL). Results: Up-regulation of NOTCH1 signaling, through either overexpression of surface NOTCH1 or acquired gain-of-function mutations, is involved in both T-ALL initiation and progression. Conclusion: Notch1 mutations contribute to leukemogenic transformation of normal T-cells. Significance: Our data provide a rationale to target both NOTCH1 and RAS signaling for T-ALL treatment.

Original languageEnglish
Pages (from-to)18219-18227
Number of pages9
JournalJournal of Biological Chemistry
Volume288
Issue number25
DOIs
StatePublished - 21 Jun 2013

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