High mTOR expression independently prognosticates poor clinical outcome to induction chemotherapy in acute lymphoblastic leukemia

  • Asheema Khanna
  • Bharat Bhushan
  • Pradeep Singh Chauhan
  • Sunita Saxena
  • Dipendra Kumar Gupta
  • Fouzia Siraj
Original Article
  • 77 Downloads

Abstract

In acute lymphoblastic leukemia (ALL), limited data are available on mTOR gene expression in clinical samples and its role in predicting response to induction chemotherapy. mRNA expression of mTOR gene was determined quantitatively by real-time PCR in 50 ALL patients (30 B-ALL and 20 T-ALL) and correlated with clinical outcome after induction chemotherapy. Expression level of mTOR was upregulated in more than 50% of cases of ALL. In T-ALL, high expression of mTOR was commonly seen, more in adults than children (82 vs. 55% cases), while in B-ALL it was same (~ 63% cases) in both adults and children. Mean fold change of mTOR expression was significantly higher in non-responders compared to responders of both adult B-ALL (7.4 vs. 2.7, p = 0.05) and T-ALL (13.9 vs. 2.4, p = 0.001). Similar results were seen in pediatric non-responders when compared to responders of both B-ALL (14.5 vs. 2.5, p = 0.006) and T-ALL (24.2 vs. 1.7, p = 0.002). Interestingly, we have observed that mTOR expression was two times higher in non-responders of children compared to adults in both B-ALL (14.5 vs. 7.4, p = 0.05) and T-ALL (24.2 vs. 13.9, p = 0.01). Multivariate analysis with other known prognostic factors revealed that mTOR expression independently predicts clinical response to induction chemotherapy in ALL. This study demonstrates that high mTOR expression is associated with poor clinical outcome in ALL and can serve as a potential target for novel therapeutic strategies.

Keywords

Acute lymphoblastic leukemia (ALL) Gene expression Induction chemotherapy Mechanistic target of rapamycin (mTOR) Multivariate analysis 

Notes

Funding

This study was supported by a grant from Department of Science and Technology (DST), Government of India.

Author’s contribution

AK designed the study, performed the experiments, drafted the paper and analyzed the data. BB analyzed the data. PSC helped in acquisition and interpretation of data. DKG contributed to diagnosis and treatment of patients. SS supervised the study and contributed to essential reagents and tools. FS designed the study, revised the paper and approved the final and submitted versions of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.National Institute of Pathology (ICMR)New DelhiIndia
  2. 2.Symbiosis School of Biomedical SciencesSymbiosis International UniversityPuneIndia
  3. 3.Department of Medical Oncology, DR.B.R, Ambedkar Institute-Rotary Cancer HospitalAll India Institute of Medical SciencesNew DelhiIndia
  4. 4.Department of HematologySafdarjung HospitalNew DelhiIndia

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