Clinical relevance of FLT3 receptor protein expression in Indian patients with acute leukemia

Vora, Hemangini H.; Shukla, Shilin N.; Brahambhatt, Birwa V; Mehta, Shalvi; Patel, Nupur; Parikh, Sonia; Shah, K.; Shah, Pankaj

doi:10.1111/j.1743-7563.2010.01322.x

Cited by 16 publications

(20 citation statements)

References 28 publications

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“…Thus, our results demonstrate that in wild type FLT3 group CD135 protein expression is equally important in predicting clinical outcome. These results strengthen findings of our previous study that CD135 protein could be of potential prognostic value in AML [25]. Similarly few studies [19,24,50] have reported high wild type FLT3 expression level as a possible risk factor.…”

supporting

confidence: 91%

“…The advantage of flow cytometry over Western blotting in protein estimation was reported by Wergeland et al [52]. Our previous study on acute leukemia [25] was the first Indian report on CD135 protein over expression in 82% of AML, 60% of B-ALL, and 23% of T-ALL by flow cytometry.…”

Section: Discussionmentioning

confidence: 79%

“…Very few studies have evaluated the possible association among FLT3 mutations, RNA expression and protein expression [19,[23][24]. In our initial study, clinical relevance of FLT3 receptor protein on intact leukemic blasts by flow cytometry was evaluated in Acute Leukemia and found frequent over expression of FLT3 protein in Acute Myeloid Leukemia and B-Acute Lymphoid Leukemia [25]. Further, in a small series of AML, the incidence of protein expression higher than FLT3 mutations was seen.…”

Section: Introductionmentioning

confidence: 96%

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Comprehensive FLT3 analysis in Indian acute myeloid leukaemia

Mehta¹,

Shukla²,

Vora³

2012

J Blood Lymph

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Aim: Activating mutations of FLT3 are commonly found in AML patients and reported to be associated with poor clinical outcome. We aimed to evaluate the incidence of FLT3 mutations along with FLT3 mRNA and CD135 protein expression in AML patients of western India and their role in prognosis of disease.Method: Analysis for the detection of FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD) point mutations and quantification of mRNA level was carried out in total 174 de novo patients diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and aplastic anemia using PCR and RT-PCR methods. FLT3 protein was quantified by flow cytometry on leukemic blasts. Results:The incidence of FLT3 ITD, FLT3 TKD mutations and CD135 protein expression was found to be 19%, 7% and 62% respectively in AML patients. In MDS, only FLT3 ITD mutation and CD135 protein over expression could be analyzed, incidence of which was 22% and 60%. In aplastic anemia, FLT3 mutations, FLT3 mRNA and protein over expression were not detected. FLT3 mutations as well as FLT3 mRNA and protein over expression were prominently noted in AML subtypes associated with myelo-monocytic lineage. CD135 protein over expression was significantly associated with reduced Disease Free Survival (DFS) whereas WBC and blasts emerged as poor prognostic factors with respect to Disease Free Survival (DFS) and Overall Survival (OS) respectively in multivariate analysis. Conclusion:Our data suggest that CD135 receptor protein over expression is a potential prognostic marker as well as molecular target for FLT3 inhibitors in AML patients.

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supporting

confidence: 91%

Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 96%

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Comprehensive FLT3 analysis in Indian acute myeloid leukaemia

Mehta¹,

Shukla²,

Vora³

2012

J Blood Lymph

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“…Then 2 ml phosphate buffered saline (PBS) was added and the samples were centrifuged at 400 g for 5 minutes. The supernatant was discarded and the pellet was resuspended in 500 µl PBS [11].…”

Section: Patientsmentioning

confidence: 99%

“…Then samples were centrifuged at 400 g for 5 minutes. The supernatant was discarded and the remaining pellet was washed twice with PBS and then resuspended in 500 µl PBS [11].…”

Section: Patientsmentioning

confidence: 99%

Overexpression of Bcl2 protein predicts chemoresistance in acute myeloid leukemia: Its correlation with FLT3

Sv¹,

Sn²,

Hh³

2014

neo

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Potential prognostic biomarkers in acute myeloid leukemia (AML) can be identified by understanding the cellular pathway and molecular changes underlying leukemogenesis. Deregulation of apoptosis is one of the important features of AML and to understand the molecular mechanism underlying apoptosis and its contribution to tumor progression, this study aimed to evaluate anti-apoptotic Bcl2 protein expression in AML and correlate with FLT3 parameters for their role in prognosis of disease.Bcl2 and FLT3 protein expression was quantified by flow cytometry on leukemic blasts in total 174 de novo AML, myelodysplastic syndrome (MDS) and aplastic anemia patients. FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD) point mutations and quantification of mRNA level was carried out using PCR and RT-PCR methods.The incidence of Bcl2 positivity was 71% in AML patients. Bcl2 positivity was significantly associated with CD34+ and CD117+ AML. Bcl2 positivity tended to be associated with reduced DFS while Bcl2 positivity with FLT3 protein positivity was significantly associated with reduced DFS. In multivariate analysis, Bcl2+ and combined Bcl2+/FLT3 protein+ along with high WBC count emerged as poor prognostic factors for reduced DFS and high blast count for predicting reduced OS. In MDS patients, the incidence of Bcl2 expression was high while in aplastic anemia patients, incidence of Bcl2 expression was low.Patients with Bcl2 and FLT3 protein positivity showed significantly reduced DFS suggesting parallel role of these proteins in imparting chemoresistance to the leukemic cells.

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FLT3, a prognostic biomarker for acute myeloid leukemia (AML): Quantitative monitoring with a simple anti‐FLT3 interaction and flow cytometric method

Ampasavate

Jutapakdee

Phongpradist

et al. 2019

Clinical Laboratory Analysis

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BackgroundOverexpression of fms‐like tyrosine kinase 3 (FLT3) protein in leukemia is highly related to poor prognosis and reduced survival rate in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. Simple but efficient quantification of FLT3 protein levels on the leukemic cell surface using flow cytometry had been developed for rapid determination of FLT3 on intact cell surface.MethodsQuantitation protocol for FLT3 biomarker in clinical samples was developed and validated. Cell model selection for calibration curve construction was identified and evaluated. Selected antibody concentrations, cell density, and incubation time were evaluated for most appropriate conditions. Comparison of the developed FLT3 determination protocol with the conventional Western blot analysis was performed.ResultsEoL‐1 cell line was selected for using as positive control cells. Calibration curve (20%‐120% of FLT3 positive cells) and quality control (QC) levels were constructed and evaluated. The results demonstrated good linearity (r 2 > 0.99). The intra‐ and inter‐day precision and accuracy, expressed as the coefficient of variation (%CV) and % recovery, were <20% and fell in 80%‐120% in all cases. When compared with Western blotting results, FLT3 protein expression levels in leukemia patient's bone marrow samples were demonstrated in the same trend.ConclusionsThe effective, reliable, rapid, and economical analytical technique using the developed flow cytometric method was demonstrated for FLT3 protein determination on leukemic cell surface. This method provided a practical analysis of FLT‐3 biomarker levels which is valuable for physician decision in acute leukemia treatment.

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Clinical relevance of FLT3 receptor protein expression in Indian patients with acute leukemia

Abstract: In summary, our data imply that there is frequent overexpression of the FLT3 protein in AML and B-ALL patients of Indian origin. In future, the FLT3 protein level may be used to select patients for whom FLT3 inhibitor therapy may be indicated.

Cited by 16 publications

References 28 publications

Comprehensive FLT3 analysis in Indian acute myeloid leukaemia

Comprehensive FLT3 analysis in Indian acute myeloid leukaemia

Overexpression of Bcl2 protein predicts chemoresistance in acute myeloid leukemia: Its correlation with FLT3

FLT3, a prognostic biomarker for acute myeloid leukemia (AML): Quantitative monitoring with a simple anti‐FLT3 interaction and flow cytometric method

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