Journal of Leukemia
Open Access

IKZF1 Mutation's Clinical Consequences on Acute Lymphoblastic Leukemia

Robert Patricia^{* *}Correspondence: Robert Patricia, Department of Pathology, National Institute of Health, Maryland, USA, Email:

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Description

The aggressive hematological cancer Acute Myeloid Leukemia (AML) is highly genetically heterogeneous. A portion of AML has been shown to have the initiation and maintenance related with common mutations or rearrangements but its pathophysiology is still not entirely understood. The studies concentrate on the IKZF1 mutation, though other recurrent genetic changes with one relatively lower frequency are undoubtedly also involved in this process. The transcription factor family of zinc finger DNA binding proteins, which also includes IKZF2, IKZF3, IKZF4 and IKZF5, includes IKZF1, which encodes IKAROS (PEGASUS). One protein with a length of 519 amino acids is encoded by the IKZF1 gene, which is located at 7p12.2 on the short arm of chromosome 7. IKZF1 has two zinc fingers at the C-terminus that are necessary for building homo- and hetero-dimerization amongst distinct IKZF proteins, in addition to four zinc fingers at the N-terminal that directly bind to DNA at the core motif A/GGAAA. A minimum of 16 isoforms have been discovered due to alternative splicing or intragenic deletion, with the exception of full-length IKZF1 (IK1). Similar to IK1, IK2 and IK3 continue to have the ability to bind DNA, whereas IK4 to IK6 lose this ability and have a predominately negative impact on full-length IKZF1. Functionally, IKZF1 regulates the lymphoid lineage's ontogeny and homeostasis and is essential for nearly every stage of normal lymphoid differentiation. IKZF1modifications primarily involve deletion and mutation. IKZF1 alterations frequently affected Acute Lymphoblastic Leukemia (ALL), where IKZF1 deletion rather than IKZF1 mutation was predominate, in line with its significant role in the lymphoid system. Additionally, IKZF1alterations were more prevalent in Philadelphia chromosome (Ph)-positive ALL and Ph-like ALL, and they gave these ALL subtypes a poor prognosis. IKZF1 alterations, in contrast, have received less attention in AML and there aren't as many studies on them. Children with pediatric AML have been found to frequently have IKZF1 deletion, which is brought on by monosomy 7 or 7p deletion. Moreover, IKZF1 mutation and monosomy 7 are more likely to be present in EVI1-rearranged AML.

IKZF1 mutation was one of the rare AML mutations, and its frequency in this cohort of newly diagnosed AML patients was 4.15% (22/530). Interestingly, studies revealed one relatively high frequency of IKZF1 mutation compared to reports from foreign countries, especially in this cohort. This behavior was possibly ascribed to two reasons: First, there were differences in the genetic backgrounds of AML among different racial groups.

Second, recent advances in sequencing depth have shown that a large number of IKZF1 mutations with low VAF (5%) were also found in our sample. Similar to IKZF1 mutation, IKZF1 impairs IKZF1 function. The prevalence of IKZF1 deletion was reported to be 3.75% (11/293) in one published study, while the frequency of IKZF1 mutation was not significantly greater than that of IKZF1 deletion, as evidenced by the low frequency of -7/monosomy 7 in our cohort (3.20%, 17/530). IKZF1 deletion was considerably more common in ALL than in AML, despite IKZF1 mutation frequency in ALL being equivalent to that in AML. According to these findings, IKZF1 deletion was the most common IKZF1 change in ALL, whereas IKZF1 mutation and IKZF1 deletion were both equally common in AML. IKZF1 mutation was therefore one major genetic change affecting IKZF1 and one significant gene mutation in AML.