Frequency and Prognostic Relevance of<i>FLT3</i>Mutations in Saudi Acute Myeloid Leukemia Patients

Elyamany, Ghaleb; Awad, M. A. El; Fadalla, Kamal; Albalawi, Mohamed; Shahrani, Mohammad Al; Abdulaaly, Abdulaziz Al

doi:10.1155/2014/141360

Cited by 18 publications

(12 citation statements)

References 35 publications

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“…On the other hand, the results revealed significant higher leukocytosis in patients with FLT3-ITD (p= 0.023) and higher blast percentage (p=0.008) compared to patients with wild-type FLT3. These findings are in accordance to previously reported (Kottaridis et al, 2001;Frohling et al, 2002;Wang et al, 2010;Su et al, 2013;Elyamany et al, 2014) but in disagreement with that reported by Shahab et al (2013).…”

Section: Discussionsupporting

confidence: 66%

Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia

Yunus¹,

Johan²,

Al‐Jamal³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis. Materials and Methods: We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia. Results: FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value = 0.008) and white blood cell count (p-value = 0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD-within 2 years (p-value = 0.374). Conclusions: The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.

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Section: Discussionsupporting

confidence: 66%

Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia

Yunus¹,

Johan²,

Al‐Jamal³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…In our study the frequency of FLT3-ITD mutation was 18.5%. Elyamany G et al14 have reported a frequency of 14.4% in the Saudi AML patients. FLT3-ITD mutations were found in 19.2% of the AML patients in Thailand by Kumsaen P et al15 However, both the studies by Elmany G et al14 and Kumsaen P et al15 have included both the paediatric and adult population while we have only studied these mutations in adults.…”

Section: Discussionmentioning

confidence: 96%

Clinico-Haematologic association and prognostic relevance of NPM1 and FLT3-ITD mutations in acute Myeloid Leukaemia

2019

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Background & Objectives: Molecular genetic abnormalities have a significant role not only in diagnosis but also in determining the clinical course and prognosis. Nucleophosmin-1 (NPM-1) is associated with good prognosis while internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) confers a poor prognosis. Knowledge of the status of these mutations in AML patients not only guides treatment decisions but also helps in predicting response to frontline induction and consolidation chemotherapy as well as the risk of relapse and overall survival. Our objectives were to determine the prevalence, clinico-haematological features and immunophenotypic characteristics of AML patients with FLT3-ITD and NPM1 mutation and to evaluate the response to induction therapy (CR) and disease free survival (DFS) in this cohort of patients. Methods: Patients diagnosed as AML from March 2015 to March 2017 at Armed Forces Institute of Pathology Rawalpindi were included in the study. Clinico-haematologic and immunophenotypic parameters were noted and molecular analysis for FLT3-ITD and NPM1 mutation was performed. Any correlation with cytogenetics or other molecular markers was also studied. Response to standard induction chemotherapy and disease-free survival were assessed. Results: A total of 108 cases of AML were analyzed. Median age was 35 years and 64.8% were males. The median age of the study group was 35 years. Of these, 70 (64.8%) were males while 38 (35.2%) were females. Twenty-nine (26.9%) patients were NPM1 positive, twelve (11.1%) were FLT3-ITD positive while eight (7.4%) were positive for both mutations. Patients with NPM1 mutations were associated with female gender, higher haemoglobin level and platelet counts while those with FLT3-ITD mutations were predominantly seen in male patients and had significantly higher WBC counts, bone marrow blasts, biopsy cellularity and LDH levels. CR rates of NPM1 positive, FLT3-ITD positive and both mutation positive groups were 72%, 60% and 71%, respectively. The median disease-free survival was significantly lower in the FLT3-ITD positive group (7.1 months) as compared to the NPM1 positive group (16.1 months). The median disease-free survival was 12 months and 11.9 months in the NPM1 positive/FLT3-ITD positive and the NPM1 negative/FLT3-ITD negative groups, respectively. Conclusion: AML patients harbouring NPM1 and FLT3-ITD mutations have distinct clinical and haematological characteristics. NPM1 mutations have a better CR and DFS as compared to FLT3-ITD group. How to cite this:Mahmood R, Altaf C, Malik HS, Khan SA. Clinico-Haematologic association and prognostic relevance of NPM1 and FLT3-ITD mutations in acute Myeloid Leukaemia. Pak J Med Sci. 2019;35(1):---------. doi: https://doi.org/10.12669/pjms.35.1.285 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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“…Blast cell count and CD34 expression had significant association with the FLT3-ITD gene mutation in AML. Some studies have also reported that the presence of FLT3-ITD gene mutation is significantly associated with the higher blast cell count and CD34 expression (7,17,18,24). Normal FLT3 and negative expression of CD34 predict a longer survival (25).…”

Section: Discussionmentioning

confidence: 99%

The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients

et al. 2020

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Scan to discover online Background & Objective: FLT3-ITD has been recently used as a molecular prognostic marker for risk classification in acute myeloid leukemia (AML) therapy. In this study we aimed to investigate the association of FLT3-ITD gene mutation with bone marrow blast cell count, CD34 expression as malignant cell burden, cyclin D1 and Bcl-xL expressions as indexes of cell proliferation and anti-apoptosis and human equilibrative nucleoside transporter 1 (hENT1) expression as cytarabine transporter during AML treatment. Methods: We investigated FLT3-ITD mutations, bone marrow blast cell count, CD34, cyclin D1, Bcl-xL and hENT1 expression in bone marrow aspirates from 22 de novo AML patients in a cross sectional study. Results: FLT3-ITD mutations were observed in 5 out of 22 de novo AML patients (22.7%). Patient with FLT3-ITD mutations had higher blast cell counts (79.5% vs 56.1%, P=0.004). In patients with FLT3-ITD mutations, CD34 and cyclin D1 expressions were higher (MFI 328.80 vs 25.78, P=0.003 and MFI 74.51 vs 57.15 P=0.005) than the patients without mutations. hENT1 expression in AML with FLT3-ITD mutation was lower (MFI 29.64 versus 56.32, P=0.0000) than in mutation-free AML. There was no significant difference in Bcl-xL expression between patients with and without mutations (P=0.61). Conclusion: A significant association was found between FLT3-ITD gene mutations in AML patients with bone marrow blast cell count, CD34, cyclin D1 and hENT1 expressions, however no association was obtained with Bcl-xL expression. These findings support the role of such mutation in pathogenesis of AMLand its contribution in rearrangement of standard therapy with cytarabine in management of AML.

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Frequency and Prognostic Relevance ofFLT3Mutations in Saudi Acute Myeloid Leukemia Patients

Cited by 18 publications

References 35 publications

Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia

Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia

Clinico-Haematologic association and prognostic relevance of NPM1 and FLT3-ITD mutations in acute Myeloid Leukaemia

The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients

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