PREVALENCE OF FLT-3 MUTATION IN ACUTE MYELOID LEUKAEMIA

Authors

  • Kinza Sabir Jinnah Hospital, Allama Iqbal Medical College, Lahore
  • Nauman Ismat Butt Chaudhary Muhammad Akram Research & Teaching Hospital, Azra Naheed Medical College, Lahore
  • Muhammad Akram Jinnah Hospital, Allama Iqbal Medical College, Lahore
  • Fahmina Ashfaq Chaudhary Muhammad Akram Research & Teaching Hospital, Azra Naheed Medical College, Lahore
  • Jawayria Sajid Jinnah Hospital, Allama Iqbal Medical College, Lahore
  • Kausar Bano Jinnah Hospital, Allama Iqbal Medical College, Lahore

Abstract

Background: FLT-3 mutation is a valuable prognostic marker in patients of AML being related with bad prognosis and poor clinical response to conventional chemotherapeutic agents. Frequency of FLT-3 mutation in AML varies from 25% to 35%. The objective of this study was to determine prevalence of FLT-3 mutation in patients with Acute Myeloid Leukaemia. Methods: This observational cross-sectional Study was conducted in Department of Oncology, Jinnah Hospital Lahore from 1st October 2018 to 31st March 2019. Patients with acute myeloid leukaemia, aged 15–60 years, of both genders were included. After taking consent, demographic data was noted. Three ml of sample of blood was obtained from each patient and sent for detection of FLT-3 mutation. Data was analysed using SPSS version 20.0. Chi square test was applied, p-value <0.05 significant. Results: A total of 180 patients were enrolled in this study. The mean±SD age of patients was 34.72±14.3 years, among which 38.3% were female and 61.7% male. The mean±SD duration of disease was 3.39±2.8 months. The mean±SD haemoglobin level, TLC and platelet counts were 7.2±2.3 g/dl, 30,913±63,573 per cm and 58.6±52.3×103 per cm. The blast cell (%) count was 69.6±19.8. FLT-3 mutation was present in 18.9%. Conclusion: We conclude that FLT-3 mutation to be present in only a minority of patients with Acute Myeloid Leukaemia having no significant association with age, sex, haemoglobin, WBCs and blast counts.

Author Biographies

Kinza Sabir, Jinnah Hospital, Allama Iqbal Medical College, Lahore

Department of Medical Oncology, Postgraduate Resident

Nauman Ismat Butt, Chaudhary Muhammad Akram Research & Teaching Hospital, Azra Naheed Medical College, Lahore

Department of Medicine, Senior Registrar

Muhammad Akram, Jinnah Hospital, Allama Iqbal Medical College, Lahore

Department of Medical Oncology, Professor

Fahmina Ashfaq, Chaudhary Muhammad Akram Research & Teaching Hospital, Azra Naheed Medical College, Lahore

Department of Medicine, Assistant Professor

Jawayria Sajid, Jinnah Hospital, Allama Iqbal Medical College, Lahore

Department of Medical Oncology, Postgraduate Resident

Kausar Bano, Jinnah Hospital, Allama Iqbal Medical College, Lahore

Department of Medical Oncology, Assistant Professor

References

Checkoway H, Dell LD, Boffetta P, Gallagher AE, Crawford L, Lees PS, et al. Formaldehyde exposure and mortality risks from acute myelogenous leukemia and other Lymphohematopoietic Malignancies in the US National Cancer Institute cohort study of workers in Formaldehyde Industries. J Occup Environ Med 2015;57(7):785–94.

Döhner H, Weisdorf DJ, Bloomfield CD. Acute myelogenous leukemia. N Engl J Med 2015;373(12):1136–52.

Cancer Genome Atlas Research Network, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013;368(2):2059–74.

Marcucci G, Haferlach T, Dohner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol 2011;29(5):475–86.

Granfeldt Østgård LS, Medeiros BC, Sengeløv H, Nørgaard M, Andersen MK, Dufva IH, et al. Epidemiology and clinical significance of secondary and therapy-related acute myelogenous leukemia: a national population-based cohort study. J Clin Oncol 2014;33(31):3641–9.

Medinger M, Lengerke C, Passweg J. Novel Prognostic and Therapeutic Mutations in Acute Myeloid Leukemia. Cancer Genomics Proteomics 2016;13(5):317–29.

Elyamany G, Awad M, Fadalla K, Albalawi M, Al Shahrani M, Al Abdulaaly A. Frequency and prognostic relevance of FLT3 mutations in saudi acute myelogenous leukemia patients. Adv Hematol 2014;2014:141360.

Smith CC, Wang Q, Chin CS, Salerno S, Damon LE, Levis MJ, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 2012;485(7397):260–3.

Allahyari A, Sadeghi M, Ayatollahi H, Yazdi HN, Tavakol M. Frequency of FLT3 (ITD, D835) Gene Mutations in Acute Myelogenous Leukemia: a Report from Northeastern Iran. Asian Pac J Cancer Prev 2016;17(9):4319–22.

Ishfaq M, Malik A, Faiz M, Sheikh I, Asif M, Khan MN, et al. Molecular characterization of FLT3 mutations in acute leukemia patients in Pakistan. Asian Pac J Cancer Prev 2012;13(9):4581–5.

Yunus NM, Johan MF, Ali Nagi Al-Jamal H, Husin A, Hussein AR, Hassan R. Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia. Asian Pac J Cancer Prev 2015;16(12):4869–72.

Rezaei N, Arandi N, Valibeigi B, Haghpanah S, Khansalar M, Ramzi M. FMS-Like Tyrosine Kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) in Iranian Adult Acute Myeloid Leukemia Patients with Normal Karyotypes: Mutation Status and Clinical and Laboratory Characteristics. Turk J Haematol 2017;34(4):300–6.

Sazawal S, Kumar B, Hasan SK, Dutta P, Kumar R, Chaubey R, et al. Haematological & molecular profile of acute myelogenous leukaemia in India. Indian J Med Res 2009;129(3):256–61.

Chauhan PS, Bhushan B, Mishra AK, Singh LC, Saluja S, Verma S, et al. Mutation of FLT3 gene in acute myeloid leukemia with normal cytogenetics and its association with clinical and immunophenotypic features. Med Oncol 2011;28(2):544–51.

Kuchenbauer F, Kern W, Schoch C, Kohlmann A, Hiddemann W, Haferlach T, et al. Detailed analysis of FLT3 expression levels in acute myeloid leukemia. Haematologica 2005;90(12):1617–25.

Lee JN, Kim HR, Shin JH, Joo YD. Prevalence of FLT3 internal tandem duplication in adult acute myelogenous leukemia. Korean J Lab Med 2007;27(4):237–43.

Pratz KW, Sato T, Murphy KM, Stine A, Rajkhowa T, Levis M. FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood 2010;115(7):1425–32.

Stone RM, Mandrekar SJ, Sanford BL, Stine A, Rajkhowa T, Levis M. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N Engl J Med 2017;377(5):454–64.

Patnaik MM. The importance of FLT3 mutational analysis in acute myeloid leukemia. Leuk Lymphoma 2018;59:2273–86.

Larrosa‐Garcia M, Baer MR. FLT3 Inhibitors in Acute Myeloid Leukemia: Current Status and Future Directions. Mol Cancer Ther 2017;16(6):991–1001.

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Published

2021-06-28