Introduction and Objective. CRLF2 overexpression (CRLF2-high) is a marker of poor prednisone response and worse relapse-free survival in acute lymphoblastic leukaemia (ALL). However, the mechanisms that lead to CRLF2-high are not fully elucidated. Recent studies have shown that IKZF1 binds to the CRLF2 promoter region, suppressing its expression via H3K9me3 recruiting to this region. IKZF1 is the founding member of a family of transcription factors composed of four other genes (IKZF2-IKZF5), that are structurally and functionally similar. At their N-terminus, the proteins of the IKAROS family have zinc fingers responsible for the specific interaction with DNA through the main sequence T/GGGAA. Based on the above information, we aim to determine which of the genes in these family may be associated with CRLF2-high in ALL. Material and Methods. Data from the TARGET database (patients diagnosed with either B-cell precursor ALL, B-ALL or T-cell ALL, T-ALL) and from B-ALL samples received in our lab at INCA were included. For TARGET, we used RNA-seq data to define the transcriptional levels of CRLF2 and IKAROS (IKZF2-5) and for our lab samples, RT-qPCR. The detection of molecular alterations in CRLF2 was performed by FISH (IGH–CRLF2, P2RY8–CRLF2 rearrangements and PAR1 region deletions) and PCR followed by sequencing (CRLF2 F232C and V249M). The pcDNATM5/FRT/TO vector will be used for cloning and expression of IKZF2 and IKZF5 and pGL4 Luciferase Reporter Vector for cloning the CRLF2 promoter region. The luciferase assay will be performed with the Dual-Luciferase® Reporter Assay system. Results and Conclusion. CRLF2 expression was evaluated for 264 patients with T-ALL (TPM) and 137 patients with B-ALL (FPKM) in TARGET, with the fourth quartile considered the group of patients with CRLF2-high. For T-ALL patients, analyses of association between CRLF2 and each member of the IKAROS family were performed. We observed that the genes IKZF1 (p=0.0004918), IKZF2 (p=0.008289), IKZF4 (p=0.04287) and IKZF5 (p=0.0001361) were differentially expressed according to the CRLF2 groups (high and low), while in B-ALL only the main IKZF5 isoform (IKZF5-201) was differentially expressed (p=0.01066). Of the 131 B-ALL samples, 33 cases were CRLF2-high, of which 18.2% had CRLF2 rearrangements, 24.4% alteration in the PAR1 region and 12.1% CRLF2 mutations. Finally, IKZF2 (RefSeq: NM_001387220.1) and IKZF5 (RefSeq: NM_001372123.1) were successfully amplified from gDNA, but we have not yet been able to efficiently clone the aforementioned genes into the pcDNATM5/FRT/TO vector. In conclusion, our preliminary data shows an association between CRLF2-high and members of the IKAROS family in T-ALL, suggesting that both might play a role in the leukaemogenesis of this leukaemia subtype. However, these results are part of an ongoing investigation and will need further investigations and validations to address our original hypothesis.