IKZF1 Alterations and Therapeutic Targeting in B-Cell Acute Lymphoblastic Leukemia

Jonathan Paolino; Harrison K Tsai; Marian H Harris; Yana Pikman

doi:10.3390/biomedicines12010089

IKZF1 Alterations and Therapeutic Targeting in B-Cell Acute Lymphoblastic Leukemia

Biomedicines. 2024 Jan 1;12(1):89. doi: 10.3390/biomedicines12010089.

Authors

Jonathan Paolino^{1

2}, Harrison K Tsai³, Marian H Harris³, Yana Pikman^{1

2}

Affiliations

¹ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
² Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
³ Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.

Abstract

IKZF1 encodes the transcription factor IKAROS, a zinc finger DNA-binding protein with a key role in lymphoid lineage development. IKAROS plays a critical role in the development of lineage-restricted mature lymphocytes. Deletions within IKZF1 in B-cell acute lymphoblastic leukemia (B-ALL) lead to a loss of normal IKAROS function, conferring leukemic stem cell properties, including self-renewal and subsequent uncontrolled growth. IKZF1 deletions are associated with treatment resistance and inferior outcomes. Early identification of IKZF1 deletions in B-ALL may inform the intensification of therapy and other potential treatment strategies to improve outcomes in this high-risk leukemia.

Keywords: B-cell acute lymphoblastic leukemia; IKAROS; IKZF1.

Publication types

Review

Grants and funding

This work is supported by Boston Children’s Hospital Translational Research Program (TRP) (J.P.), Wong Family Award in Translational Oncology (J.P.), Alex’s Lemonade Stand Foundation (J.P.), Hyundai Hope on Wheels Scholar grant (Y.P.), Julia’s Legacy of Hope St. Baldrick’s Foundation Consortium Research Grant (Y.P.).