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Prevalence and Clinical Significance of FLT3 and NPM1 Mutations in Acute Myeloid Leukaemia Patients of Assam, India

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Abstract

Acute Myeloid Leukaemia (AML) is one of the common forms of haematological malignancy in adults. We analysed the prevalence and clinical significance of FMS-like tyrosine kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) mutations in AML patients of North East India. Co-prevalence and clinical significance of three recurrent chromosomal translocations namely t(15; 17), t(8; 21), t(16; 16) and expression of epidermal growth factor receptor (EGFR), flow markers were also documented and co-related with disease progress. We analysed bone marrow aspirates or peripheral blood samples from 165 newly diagnosed AML patients. All clinical samples were analysed by Real Time PCR and DNA sequencing based assays. NPM1 was the most frequently detected mutation in the study population (46/165 = 27.90%, 95% CI 20.75–35.05). FLT3 mutations were detected in 27/165 (16.40%, 95% CI 10.45–22.35) patients with internal tandem duplication (FLT3-ITD) in 24/165 (14.60%, 95% CI 8.91–20.29) and FLT3-D835 in 3/165 (1.80%, 95% CI 0–4.13) patients. NPM1 mutations were associated with a higher complete remission rate and longer overall survival (P < 0.01) compared to FLT3-ITD whereas FLT3-ITD showed adverse impact with poor survival rate (P < 0.01), leukocytosis (P < 0.01) and a packed bone marrow. EGFR expression was more in patients with NPM1 mutation compared to FLT3 mutation (P = 0.09). Patients with FLT3 and NPM1 mutations uniformly expressed CD13 and CD33 whereas CD34 was associated with poor prognosis (P ≤ 0.01) in patients with NPM1 mutation. FLT3-ITD was associated with inferior overall survival. However the clinical significance of FLT3-D835 was not clear due to small number of samples. NPM1 mutation showed better prognosis with increased response to treatment in the absence of FLT3-ITD.

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Abbreviations

FLT3:

FMS-like tyrosine kinase 3

NPM1:

Nucleophosmin 1

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Acknowledgements

The authors are thankful to Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India for their financial assistance for this project.

Funding

This study was financially supported by a grant from Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India (Grant Number BT/348/NE/TBP/2012).

Author Contributions

All authors listed have contributed to the work and agreed to submit the manuscript for publication.

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Author notes

  1. Jina Bhattacharyya and Sukanta Nath have contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Haematology, Gauhati Medical College and Hospital, Guwahati, Assam, India

    Jina Bhattacharyya

  2. Department of Bioengineering and Technology, Gauhati University, Guwahati, Assam, 781014, India

    Sukanta Nath, Kandarpa Kumar Saikia & Dushyant Kumar

  3. Department of Haematology, All India Institute of Medical Sciences, New Delhi, India

    Renu Saxena & Sudha Sazawal

  4. Department of Statistics, Dibrugarh University, Dibrugarh, Assam, India

    Manash Pratim Barman

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  1. Jina Bhattacharyya
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Correspondence to Kandarpa Kumar Saikia.

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Research Involving Human Participants and/or Animals

This study involves blood and bone marrow aspirates from AML patients. Ethical approval was obtained from institutional ethics committee (GUEC-12/2015) to conduct the study.

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

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee.

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Bhattacharyya, J., Nath, S., Saikia, K.K. et al. Prevalence and Clinical Significance of FLT3 and NPM1 Mutations in Acute Myeloid Leukaemia Patients of Assam, India. Indian J Hematol Blood Transfus 34, 32–42 (2018). https://doi.org/10.1007/s12288-017-0821-0

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