INTRODUCTION AND OBJECTIVES: B-cell precursor acute lymphoblastic leukaemia (B-ALL) can be classified by the occurrence of several primary genetic alterations. Recently, a new subgroup – named IKZF1plus – was associated with a worse prognosis and a higher risk of relapse in both paediatric and adult B-ALL cases. This subgroup presents a genetic profile defined by the co-occurrence of IKZF1 deletion and CDKN2A, CDKN2B (homozygous), PAX5 or PAR1 deletion, in the absence of ERG alteration. Herein, we aim to identify cellular markers that could be used for the prediction of the IKZF1plus group. MATERIAL AND METHODS: Two independent case series (TARGET and MECS) are being evaluated. The majority of patients were male (60%) and aged ≤21 years-old in both case series. The patients from our lab were all diagnosed between 2018 and 2019. We used the TARGET database (WGS, RNA-seq and clinical data) for the and characterize the groups of patients: IKZF1plus, IKZF1del and IKZF1wild. The retrospective and prospective molecular characterization of samples from our lab is performed by conventional and digital MLPA. The chi-square and Fisher tests were used to verify the statistical significance of the association between the different variables evaluated. Values of P <0.05 were considered statistically significant. RESULTS AND CONCLUSION: A total of 125 patients from TARGET were included, which were grouped as IKZF1plus (13%), IKZF1del (9%) and IKZF1wild (78%). In consequence of an enrichment of IKZF1plus cases in the B-others subgroup, we used this subgroup to perform differential expression analyses using DESeq2 to compare the three IKZF1 groups. Four genes showed increased expression, while thirteen had decreased expression in the IKZF1plus group vs the others. Among these differentially expressed genes (DEG), those that encode membrane proteins were KCNA5, GREB1, EPOR, SDK1 and PTPRB. Moreover, CRLF2 had the highest expression when comparing IKZF1plus vs wild-type. So far, 108 patients from our lab have been molecularly characterized with 15.5%, 18.5% and 63.8% being grouped as IKZF1plus, IKZF1del and IKZF1wild, respectively. Digital MLPA analyses showed an increase in the frequency of VPREB1 deletions in patients with IKZF1plus and IKZF1del. We identified that KCNA5, GREB1, EPOR, SDK1 and PTPRB are potential biomarkers to identify the IKZF1plus subgroup. Among DEG, those that encode membrane proteins, such as the 5 biomarkers mentioned above, are the best candidate to be used as markers for immunophenotyping analyses. Furthermore, CRLF2 expression might be a good candidate marker to identify this subtype.