Examination of the FLT3 and NPM1 mutational status in patients with acute myeloid leukemia from southeastern Poland

Koczkodaj, Dorota; Zmorzyński, Szymon; Michalak-Wojnowska, Małgorzata; Wąsik-Szczepanek, Ewa; Filip, Agata

doi:10.5114/aoms.2015.49811

Cited by 7 publications

(8 citation statements)

References 38 publications

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“…In patients with FLT3 and NPM1 mutations, the associations of other genetic alterations have also been evaluated to understand any possible role in disease outcome. The prevalence of FLT3 and NPM1 mutations found in this population was in coherence with other studies (Asian and Western) despite geographic and ethnic differences (Tables 3, 4) [19][20][21][22][23][24][25][26][27][28][29][30].…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…[21][22][23] However, it was higher in South Korea (22.4%) and Australia (30.8%), while it was lower in Poland (8%) and Saudi Arabia (11.6%). [24][25][26][27] In line with many previously published studies, 28,30 it was reported that t (15,17) and chromosome 8 trisomy were the most significant recurrent alterations associated with FLT3-ITD mutation. Our data showed that most of all patients with FLT3-ITD mutation had t(15,17) followed by t(8:21).…”

Section: Discussionsupporting

confidence: 57%

<p>Combined Expression of CD34 and FLT3-Internal Tandem Duplication Mutation Predicts Poor Response to Treatment in Acute Myeloid Leukemia</p>

Abdellateif¹,

Kassem²,

El-Meligui³

2020

IJGM

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Background: Acute myeloid leukemia (AML) is a common hematological malignancy associated with different cytogenetic and genetic abnormalities. Methods: FLT3-internal tandem duplication (FLT3/ITD) mutation and CD34 expression levels were assessed in the bone marrow (BM) aspirates of 153 de novo AML patients. Data were correlated with relevant clinic-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall free survival (OS) rates. Results: FLT3-ITD mutation was detected in 27/153 (17.6%) AML patients (P=0.001), and CD34 was expressed in 83/153 (54.2%) patients (P=0.293) compared to those with wild FLT3 and CD34 − expression, respectively. Patients with FLT3-ITD mutation showed increased peripheral blood and BM blast cells, abnormal cytogenetics, poor DFS and OS compared to those with wild FLT3 (P=0.013, P<0.001, P=0.010, P=0.008 and P=0.004, respectively), while there was no significant association with response to treatment (P=0.081). There was no significant association between CD34 expression and response to treatment, DFS, and OS (P>0.05). FLT3-ITD mutation and FAB subtypes were independent prognostic factors for DFS. Older age ≥39 years, HB <7 mg/dL PB blast ≥54%, and FLT3-ITD mutation were independent prognostic factors for poor OS in AML patients. The presence of both FLT3-ITD mutation and CD34 expression associated significantly with resistance to therapy (P=0.024), short DFS and OS rates (P=0.006, P=0.037, respectively). Conclusion: Combined expression of both FLT3-ITD mutation and CD34 expression is an important prognostic and predictive factor for poor disease outcome in AML patients.

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“…8,21 The t(8;21) is less frequent among the AML M2 patients in Singapore (14.5%), Australia (15.3%) and North America (22%). 13,23,24 In this study, significant difference was found in case of inv (16) 25 In an Iranian study, Rezaei et al divided the patients into FAB M3 and non-M3 groups and analysed the FLT3-ITD and NPM1 mutational status among these patients. 26 They also found that these mutations were more frequent in non-M3 patients.…”

Section: Resultsmentioning

confidence: 58%

“…FLT3-ITD mutation was found more frequently in M4 subtype in this study. Similarly, another study carried out byKoczkodaj et al (2016) in Southeastern Poland found the highest frequency of FLT3-ITD mutation in AML M4 cases.…”

mentioning

confidence: 62%

Cytogenetic Pattern in Adult Patients with de novo Acute Myeloid Leukaemia: A Single Centre Study in Bangladesh

Baqi¹,

Munmun²,

Khan³

et al. 2020

Haematol J Bangladesh

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Background: Cytogenetic analysis performed at diagnosis is considered to be the most important prognostic factor in AML. Objective: The purpose of this study was to observe the pattern of cytogenetic abnormalities in adult patients with de novo AML. Method: Total fifty-two newly diagnosed de novo AML patients were selected for the study. Six cytogenetic abnormalities including t(8;21), t(15;17), inv(16), BCR-ABL1, FLT3-ITD & NPM1 mutations were detected by Real-Time PCR. Results: In this study, 36 (69.2%) patients showed different cytogenetic abnormalities. The t(15;17) was found to be the most common. t(15;17), t(8;21) and inv(16) were found only in M3, M2 and M4 FAB subtypes, respectively. Significant association was found with increasing age and cytogenetic risk groups. BCR-ABL1 mutation showed significant relation with increased age. FLT3-ITD mutation showed significant association with increased WBC count and inv16 was significantly associated with relatively less bone marrow blast percentage. Conclusion: Cytogenetic study should be performed routinely in all cases of AML for proper diagnosis, prediction of prognosis and implementation of effective therapeutic measures.

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Examination of the FLT3 and NPM1 mutational status in patients with acute myeloid leukemia from southeastern Poland

Cited by 7 publications

References 38 publications

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

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

<p>Combined Expression of CD34 and FLT3-Internal Tandem Duplication Mutation Predicts Poor Response to Treatment in Acute Myeloid Leukemia</p>

Cytogenetic Pattern in Adult Patients with de novo Acute Myeloid Leukaemia: A Single Centre Study in Bangladesh

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