Frequency of FLT3/ITD Mutation in Patients with Acute Myeloid Leukaemia presenting at Combined Military Hospital, Rawalpindi
DOI:
https://doi.org/10.51253/pafmj.v73i6.7277Keywords:
Acute myeloid leukemia, AML prognosis, FLT3/ITD mutationAbstract
Objective: To assess the frequency of FLT3/ITD mutation in patients of Acute myeloid leukaemia presenting at Combined
Military Hospital, Rawalpindi Pakistan.
Study Design: Cross-sectional study.
Place and Duration of Study: Oncology Department, Combined Military Hospital, Rawalpindi Pakistan, from Jan to Jun 2020.
Methodology: A sample of 46 patients with acute myeloid leukaemia was included using a non-probability, consecutive
sampling technique. Genetic testing was done on all blood samples to identify FLT3-ITD mutation.
Results: Out of 46, 10(21.7%) were females and 36(78.3%) were males. The FLT3/ITD mutation frequency in our study sample was 10(21.7%), with all in de-novo AML patients and none in secondary AML. White cell count (55x109), bone marrow blasts (85%) and peripheral smear blasts (75%) were high in the FLT3-ITD mutated group in comparison to the non-mutated group.
Conclusion: Timely detection of FLT3/ITD mutation and an amplification of induction therapy would benefit this group of
patients.
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Winer ES, Stone RM. Novel therapy in Acute myeloid leukemia
(AML): moving toward targeted approaches. Ther adv Hematol
; 10: 1-18. https://doi.org/10.1177/2040620719860645
Gui P, Bivona TG. Stepwise evolution of therapy resistance in
AML. Cancer Cell 2021; 39(7): 904-906.
https://doi.org/10.1016/j.ccell.2021.06.004.
Hunter AM, Sallman DA. Current status and new treatment
approaches in TP53 mutated AML. Best Pract Res Clin Haematol
; 32(2)134-144. https://doi.org/10.1016/j.beha.2019.05.004.
Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR,
Büchner T, et al. Diagnosis and management of AML in adults:
ELN recommendations from an international expert panel.
Blood 2017; 129(4): 424-447.
https://doi.org/10.1182/blood-2016-08-733196.
Desai P, Mencia-Trinchant N, Savenkov O, Simon MS, Cheang G,
Lee S, et al. Somatic mutations precede acute myeloid leukemia
years before diagnosis. Nat Med 2018; 24(7): 1015-1023.
https://doi.org/10.1038/s41591-018-0081-z.
Bhanumathy KK, Balagopal A, Vizeacoumar FS, Vizeacoumar FJ,
Freywald A, Giambra V, et al. Protein Tyrosine Kinases: Their
Roles and Their Targeting in Leukemia. Cancers 2021; 13(2): 184.
https://doi.org/10.3390/cancers13020184.
Kiyoi H, Kawashima N, Ishikawa Y. FLT3 mutations in acute
myeloid leukemia: Therapeutic paradigm beyond inhibitor
development. Cancer Sci 2020; 111(2): 312-322.
https://doi.org/10.1111/cas.14274.
Tsapogas P, Mooney C, Brown G, Rolink A. The Cytokine Flt3-
Ligand in Normal and Malignant Hematopoiesis. Int J Mol Sci
; 18(6): 1115. https://doi.org/10.3390/ijms18061115.
Wu M, Li C, Zhu X. FLT3 inhibitors in acute myeloid leukemia. J
Hematol Oncol 2018; 11(1): 133.
https://doi.org/10.1186%2Fs13045-018-0675-4.
Ali A, Siddique MK, Shakoori AR. Frequency of FLT3/ITD
Mutations in Pakistani Acute Myeloid Leukemia Patients.
Pakistan J Zool 2013; 45(2): 495-501.
Yu J, Li Y, Zhang D, Wan D, Jiang Z. Clinical implications of
recurrent gene mutations in acute myeloid leukemia.Exp
Hematol Oncol 2020; 9(4): 2162-3619.
https://doi.org/10.1186%2Fs40164-020-00161-7.
Orgueira AM, Raindo AP, Lopez MC, Rodriguez BA, Arias JAD,
Ferro RF, et al. Gene expression profiling identifies FLT3
mutation-like cases in wild-type FLT3 acute myeloid
leukemia. PLoS One 2021 16(2): e0247093.
https://doi.org/10.1371/journal.pone.0247093
Thiede C, Steudel C, Mohr B, Schaich M, Schäkel U, Platzbecker
U, et al. Analysis of FLT3-activating mutations in 979 patients
with acute myelogenous leukemia: association with FAB
subtypes and identification of subgroups with poor prognosis.
Blood 2002; 99(12): 4326–4335.
https://doi.org/10.1182/blood.v99.12.4326.
Liang DC, Shih LY, Hung IJ, Yang CP, Chen SH, Jaing TH, et al.
Clinical relevance of internal tandem duplication of the FLT3
gene in childhood acute myeloid leukemia. Cancer 2002; 94(12):
–3298. https://doi.org/10.1002/cncr.10598.
Fröhling S, Schlenk RF, Breitruck J, Benner A, Kreitmeier S, Tobis
K, et al; AML Study Group Ulm. Acute myeloid leukemia.
Prognostic significance of activating FLT3 mutations in younger
adults (16 to 60 years) with acute myeloid leukemia and normal
cytogenetics: a study of the AML Study Group Ulm. Blood 2002;
(13): 4372–4380. https://doi.org/10.1182/blood-2002-05-1440.
Wang L, Lin D, Zhang X, Chen S, Wang M, Wang J, et al.
Analysis of FLT3 internal tandem duplication and D835
mutations in Chinese acute leukemia patients. Leukemia Res
; 29(12): 1393–1398.
https://doi.org/10.1016/j.leukres.2005.05.013.
Auewarakul U, Sritana N, Limwongse C, Thongnoppakhun W,
Yenchitsomanus PT. Mutations of the FLT3 gene in adult acute
myeloid leukemia: determination of incidence and identification
of a novel mutation in a Thai population. Cancer Genet
Cytogenet 2005; 162(2): 127–134.
https://doi.org/10.1016/j.cancergencyto.2005.03.011.
Gari M, Abuzenadah A, Chaudhary A, Al-Qahtani M, Banni H,
Ahmad W, et al. Detection of FLT3 oncogene mutations in acute
myeloid leukemia using conformation sensitive gel
electrophoresis. Int J Mol Sci 2008; 9(11): 2194–2204.
https://doi.org/10.3390%2Fijms9112194.
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–
https://doi.org/10.7314/apjcp.2012.13.9.4581.
Zaker F, Mohammadzadeh M, and Mohammadi M. Detection of
KIT and FLT3 mutations in acute myeloid leukemia with
different subtypes. Arch Iran Med 2010; 13(1): 21–25.
Sheikhha MH, Awan A, Tobal K, Liu Yin JA. Prognostic
significance of FLT3 ITD and D835 mutations in AML patients.
Hematol J 2003; 4(1): 41–46.
https://doi.org/10.1038/sj.thj.6200224.
Xu YY, Gao L, Ding Y, Sun JZ, Wang N, Wang LL, et al.
[Detection and clinical significance of FLT3-ITD gene mutation in
patients with acute myeloid leukemia]. Zhongguo Shi Yan Xue
Ye Xue Za Zhi 2012; 20(6): 1312-1315.
Al-Tonbary Y, Mansour AK, Ghazy H, Elghannam DM, AbdElghaffar HA. Prognostic significance of foetal-like tyrosine
kinase 3 mutation in Egyptian children with acute leukaemia. Int
J Lab Hematol 2009; 31(3): 320–326.
https://doi.org/10.1111/j.1751-553x.2008.01039.x.
Kottaridis PD, Gale RE, Frew ME. The presence of a FLT3
internal tandem duplication in patients with acute myeloid
leukemia (AML) adds important prognostic information to
cytogenetic risk group and response to the first cycle of
chemotherapy: analysis of 854 patients from the United Kingdom
Medical Research Council AML 10 and 12 trials. Blood 2001;
(6): 1752-1729. https://doi.org/10.1182/blood.v98.6.1752.
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