Current Hematologic Malignancy Reports

, Volume 8, Issue 1, pp 22–27

GS-1101: A Delta-Specific PI3K Inhibitor in Chronic Lymphocytic Leukemia

Chronic Leukemias (S O’Brien, Section Editor)

DOI: 10.1007/s11899-012-0142-1

Cite this article as:
Macias-Perez, I.M. & Flinn, I.W. Curr Hematol Malig Rep (2013) 8: 22. doi:10.1007/s11899-012-0142-1


Chronic lymphocytic leukemia (CLL) remains an incurable B-cell malignancy with many unanswered questions. While the cell of origin and etiology are still unknown, significant scientific progress has revealed numerous molecular targets for novel therapeutic interventions. Phosphatidylinositol 3-kinases (PI3K) regulate key cellular functions, including growth, survival and migration, by integrating and transmitting signals from diverse surface molecules including the B-cell receptor (BCR). In lymphocytes, the PI3Kδ isoform plays a critical role in B-cell homeostasis and function. In CLL, the PI3K pathway is constitutively active and dependent on PI3Kδ. GS-1101 is a highly selective PI3Kδ inhibitor that in CLL patients causes a rapid and sustained reduction in lymphadenopathy, accompanied by transient lymphocytosis. This article will review new insights into the pathophysiology of CLL, the preclinical rationale of a PI3Kδ inhibitor in CLL, and the clinical evidence supporting this first-in-class therapeutic target for CLL patients.


Signaling pathwaysB-cell receptorBCRChronic lymphocytic leukemiaCLLNew targetsPI3-KinaseCAL-101, GS-1101PI3K deltaPI3KMicroenvironment

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Hematologic Malignancies ResearchSarah Cannon Research InstituteNashvilleUSA
  2. 2.Sarah Cannon Research InstituteNashvilleUSA
  3. 3.Hematologic Malignancies ResearchThe Sarah Cannon Research InstituteNashvilleUSA