Diagnosis

R. Deshpande, Aishwarya P. Joshi, N. Tandel, R. Tyagi
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Abstract

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.
诊断
IKAROS是一种由IKZF1基因编码的锌指转录因子蛋白,对人类造血至关重要。IKZF1的功能突变缺失与成人和儿童B细胞急性淋巴母细胞白血病(B- all)有关。我们的目的是评估IKAROS蛋白表达和IKZF1 mRNA转录物在B-ALL患者中的发生率。用流式细胞术检测34例新生B-ALL患者的IKAROS蛋白表达,用RT-PCR法检测13例患者的IKZF1 mRNA转录本。分析IKAROS蛋白和IKZF1亚型的表达水平,并将其与临床和血液学参数相关联。仅存在IK-6亚型的B-ALL患者WBC计数、母细胞计数(>85%)以及祖细胞标记物CD34和Tdt阳性相关。低血红蛋白和CD19阳性与IKAROS蛋白过表达有显著相关性。在其中一名患者中,我们只发现了09%的IKAROS蛋白,有两个显性阴性亚型IK-4和IK-6,缺乏正常亚型,这可能表明疾病具有侵袭性。然而,流式细胞术方法对IKAROS蛋白的评价应与更多B-ALL患者的IKAROS亚型相关联,从而建立IKAROS蛋白的临床相关性。与传统预后标志物的相关性提示,出现IK-6亚型的患者可被认为是高危患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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