Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia

Pazhakh, Vahid; Zaker, Farhad; Atashrazm, Farzaneh

doi:10.4103/0256-4947.75778

Cited by 7 publications

(6 citation statements)

References 33 publications

(45 reference statements)

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“…This result was higher than previously reported findings. [37][38][39][40][41][42][43] However, our results are in accordance with other Egyptian (48.3%), 44 (45.8%) 45 and Iraqi (46.88%) 46 studies. These differences may be attributed to difference in method of detection, sample size, ethnic, racial, environmental, and geographical factors.…”

Section: Discussionsupporting

confidence: 80%

Prognostic impact ofWilms tumorgene mutations in Egyptian patients with acute myeloid leukemia with normal karyotype

2013

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The Wilms' tumor (WT1) gene mutations were detected in patients with most forms of acute leukemia. However, the biological significance and the prognostic impact of WT1 mutation in Egyptian patients with acute myeloid leukemia with normal karyotype (AML-NK) are still uncertain. We aimed to evaluate the incidence and clinical relevance of WT1 gene mutations in acute myeloid leukemia with normal karyotype (AML-NK). Exons 7 and 9 of WT1 were screened in samples from 216 adult NK-AML using polymerase chain reaction single-strand conformation polymorphism techniques. Twenty-three patients (10.6%) harbored WT1 mutations. Younger ages and higher marrow blasts were significantly associated with WT1 mutations (P = 0.006 and 0.003 respectively). Complete remission rates were significantly lower in patients with WT1 mutations than those with WT1 wild-type (P = 0.015). Resistance, relapse, and mortality rates were significantly higher in patients with WT1 mutations than those without (P = 0.041, 0.016, and 0.008 respectively). WT1 mutations were inversely associated with NPM1 mutations (P = 0.007). Patients with WT1 mutations had worse disease-free survival (P < 0.001) and overall survival (P < 0.001) than patients with WT1 wild-type. In multivariable analyses, WT1 mutations independently predicted worse DFS (P < 0.001; hazard ratio [HR] 0.036) and overall survival (P = 0.001; HR = 0.376) when controlling for age, total leukocytic count (TLC), and NPM1 mutational status. In conclusion, WT1 mutations are a negative prognostic indicator in intensively treated patients with AML-NK, may be a part of molecularly based risk assessment and risk-adapted treatment stratification of patients with AML-NK.

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Section: Discussionsupporting

confidence: 80%

Prognostic impact ofWilms tumorgene mutations in Egyptian patients with acute myeloid leukemia with normal karyotype

2013

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“…The incidence of FLT3-ITD+ in the current study was 15.9%, which is obviously similar incidences having been previously reported in some studies (Table 5) (Elyamany et al, 2014;Aly et al, 2012;Pazhakh et al, 2011). Several studies observed a lower incidence of FLT3-ITD+ than in our study (Elyamany et al, 2014;Aly et al, 2012;Pazhakh et al, 2011;Ishfaq et al, 2002;Gari et al, 2008;Sheikhha et al, 2003). Various studies have detected a high occurrence of FLT3-ITD+ (Thiede et al, 2002;Xu et al, 2012;Wang et al, 2010;Al-tonbary et al, 2009;Suzuki et al, 2007;Wang et al, 2005;Auewarakul et al, 2005;Fröhling et al, 2002).…”

Section: Discussionsupporting

confidence: 91%

“…Adult studies have shown a prevalence of 25-30% for the FLT3-ITD+ in AML patients who have no cytogenetic abnormalities (Schnittger et al, 2002;Patnaik 2018;Griffith et al, 2004) and ~7% for FLT3-KTD point mutation of the activation loop domain (Bacher et al, 2008;Yamamoto et al, 2001;Kim 2010). The incidence of FLT3-ITD+ in the current study was 15.9%, which is obviously similar incidences having been previously reported in some studies (Table 5) (Elyamany et al, 2014;Aly et al, 2012;Pazhakh et al, 2011). Several studies observed a lower incidence of FLT3-ITD+ than in our study (Elyamany et al, 2014;Aly et al, 2012;Pazhakh et al, 2011;Ishfaq et al, 2002;Gari et al, 2008;Sheikhha et al, 2003).…”

Section: Discussionsupporting

confidence: 88%

Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype

Alarbeed

Wafa

Moassass

et al. 2021

Asian Pac J Cancer Prev

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Objective: Activating mutations of the fms-like tyrosine kinase 3 gene ( FLT3 ) by internal tandem duplications (ITDs) in the juxtamembrane domain (JMD) have been reported in ~30% of adult acute myeloid leukemia (AML) patients with cytogenetically normal karyotype (CN). However, FLT3 /ITD mutations are frequently accompanied with leukocytosis, high percentage of blasts in bone marrow (BM), and increased the risk of treatment failure in AML patients. FLT3 -ITD mutated AML patients mainly with normal karyotype have higher relapse probability and shorter duration of complete remission (CR) after chemotherapy, so FLT3 -ITD mutation is considered as an independent poor prognostic factor in AML. Methods: FLT3 -ITD and FLT3 -KTD were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism- PCR (RFLP-PCR) in 44 adults AML patients with cytogenetically normal karyotype (AML-CN) at diagnosis to characterize FLT3 status. The results were correlated with the prognostic factors. Results: In this study, FLT3 -ITD mutations were identified in 7 (15.9%) of the 44 AML-CN patients. Among the 7 patients with FLT3 /ITD mutations, 6 patients revealed a typical ITDs mutation (fragment size was 329 bp) and one patient showed untypical ITD mutation (fragment size was ~400 bp). Whereas 37 patients (61.7%) were FLT3 -ITD. None of all AML-CN patients examined showed FLT3 -KTD mutations. Conclusions: Our results support that FLT3 -ITD are independent adverse prognostic factors for elderly AML-CN patients and are associated with low overall survival (OS), low rate of CR, high relapse rate (RR), and high percentage of BM blast at diagnosis. We concluded, FLT3 mutation analysis should be performed as a routine test in AML-CN patients.

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“…FLT3-ITD mutations (exon 14-15) were analysed on genomic DNA by PCR amplification as previously described [17]. In the absence of FLT3-ITD a fragment of 329 bp was detected in wild-type FLT3 gene whereas additional upper band (higher molecular weight band) was observed in cases with FLT3-ITD mutation (Fig.…”

Section: Detection Of Flt3 and Npm1 Mutationsmentioning

confidence: 99%

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

Bhattacharyya

Nath

Saikia

et al. 2017

Indian J Hematol Blood Transfus

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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 ( < 0.01) compared to FLT3-ITD whereas FLT3-ITD showed adverse impact with poor survival rate ( < 0.01), leukocytosis ( < 0.01) and a packed bone marrow. EGFR expression was more in patients with NPM1 mutation compared to FLT3 mutation ( = 0.09). Patients with FLT3 and NPM1 mutations uniformly expressed CD13 and CD33 whereas CD34 was associated with poor prognosis ( ≤ 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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Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia

Cited by 7 publications

References 33 publications

Prognostic impact ofWilms tumorgene mutations in Egyptian patients with acute myeloid leukemia with normal karyotype

Prognostic impact ofWilms tumorgene mutations in Egyptian patients with acute myeloid leukemia with normal karyotype

Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype

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

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