Diagnosis

Summary IKAROS, a zinc finger transcription factor protein encoded by the IKZF1 gene is crucial for hematopoiesis in humans. Loss of function mutations in IKZF1 have been implicated in adult and pediatric B cell Acute Lymphoblastic Leukemia (B-ALL). Our aim is to evaluate the incidence of IKAROS protein expression and IKZF1 mRNA transcripts in B-ALL patients. IKAROS protein expression was evaluated in total 34 patients diagnosed as de-novo B-ALL using flow cytometry and IKZF1 mRNA Transcripts were detected using reverse transcriptase - polymerase chain reaction (RT-PCR) method in 13 patients. The expression levels of the IKAROS protein and IKZF1 isoforms were analysed and correlated with clinical and hematological parameters. B-ALL patients with presence of only IK-6 isoform were associated with high WBC count, blast count (>85%) as well as progenitor cell markers CD34 and Tdt positivity. Also there was a significant correlation of low hemoglobin and CD19 positivity with IKAROS protein over expression. In one of the patient we found only 09% of IKAROS protein, having two dominant negative isoforms IK-4 and IK-6 with absence of normal isoforms, which might suggest disease aggressiveness. However, IKAROS protein evaluation by flow cytometry method should be correlated with IKAROS isoforms in more number of B-ALL patients so that the clinical relevance of IKAROS protein could be established. Correlation with conventional prognostic markers suggests that the patients showing the presence of IK-6 isoform can be considered as high risk patients.