IKZF1 Alterations and Therapeutic Targeting in B-Cell Acute Lymphoblastic Leukemia.
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ABSTRACT:
SUBMITTER: Paolino J
PROVIDER: S-EPMC10813044 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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<i>IKZF1</i> Alterations and Therapeutic Targeting in B-Cell Acute Lymphoblastic Leukemia.
Paolino Jonathan J Tsai Harrison K HK Harris Marian H MH Pikman Yana Y
Biomedicines 20240101 1
<i>IKZF1</i> 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 <i>IKZF1</i> 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. <i>IKZF1</i> deletions are associated with treatment ...[more]
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Project description:Transcription factor IKZF1 (IKAROS) acts as a critical regulator of lymphoid differentiation and is frequently deleted or mutated in B-cell precursor acute lymphoblastic leukemia. IKZF1 gene defects are associated with inferior treatment outcome in both childhood and adult B-cell precursor acute lymphoblastic leukemia and occur in more than 70% of BCR-ABL1-positive and BCR-ABL1-like cases of acute lymphoblastic leukemia. Over the past few years, much has been learned about the tumor suppressive function of IKZF1 during leukemia development and the molecular pathways that relate to its impact on treatment outcome. In this review, we provide a concise overview on the role of IKZF1 during normal lymphopoiesis and the pathways that contribute to leukemia pathogenesis as a consequence of altered IKZF1 function. Furthermore, we discuss different mechanisms by which IKZF1 alterations impose therapy resistance on leukemic cells, including enhanced cell adhesion and modulation of glucocorticoid response.
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