IK6 isoform with associated cytogenetic and molecular abnormalities in Chinese patients with Philadelphia chromosome-positive adult acute lymphoblastic leukemia

Abstract

The IK6 isoform plays an important role in Philadelphia chromosome-positive adult acute lymphoblastic leukemia (Ph + ALL). This study was designed to monitor the expression of the IK6 isoform with associated cytogenetic and molecular abnormalities. The IK6 isoform, cytogenetic and molecular abnormalities were detected in 100 Chinese patients with de novo Ph+ adult ALL. Expression levels of the IK6 isoform and BCR–ABL1 transcripts were monitored during treatment. BCR–ABL1 mutation was identified in 45 paired samples. Strong correlations were found between the expression status of the IK6 isoform and blast cells, additional cytogenetic abnormalities, BCR–ABL1 transcripts, increased risk of relapse, shorter relapse-free survival and overall survival at diagnosis. Higher frequencies of single IK6 expression and ABL mutation, including the types and shifts thereof, were confirmed in relapsed patients. Furthermore, expression of the IK6 isoform was dynamically consistent with BCR–ABL1 transcript levels during treatment in the single expression group, whereas no such correlation was observed in the co-expression group. The expression pattern of the IK6 isoform was altered in three patients from the co-expression group. The findings of this study in Chinese patients with Ph+ adult ALL exhibit some discrepancies with data reported in other countries, thereby enhancing current knowledge on the therapeutic response and prognosis of this disease.

Keywords::

• IK6
• karyotype
• mutation
• relapse
• acute lymphoblastic leukemia
• adult

Acknowledgements

We thank Mrs. J. L. Pan for assisting in cytogenetic analysis, Prof. D. P. Wu for provision of clinical information and Prof. C. H. G. Ruan for his kind support. We acknowledge all members of the Jiangsu Institute of Hematology for their support.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was partially supported by grants from National Key Scientific Projects of China (2011CB933501), the National Natural Scientific Foundation of China (81070402), the Priority Academic Program for Development of Jiangsu Higher Education Institutions, Jiangsu Province's Outstanding Medical Academic Leader Program (LJ201138) and the Program for social development in Suzhou (sys201121).