High Transcript Level of FLT3 Associated with High Risk of Relapse in Pediatric Acute Myeloid Leukemia

Kang, Hyoung Jin; Lee, Ji Won; Kho, Sang Hyeok; Kim, Min Jeong; Seo, Young Jin; Kim, Hyery; Shin, Hee Young; Ahn, Hyo Seop

doi:10.3346/jkms.2010.25.6.841

Cited by 17 publications

(16 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…reported high FLT3 transcript level to be a poor prognostic factor in pediatric patients, but this study included only 5 patients in the highest FLT3 transcript expression level group. (39) Our results with CD135 MFI are in agreement with those from Kuchenbauer et al ., which showed that FLT3 transcript levels do not significantly affect OS or EFS, however they did observe a trend towards lower survival in the subset of FLT3 /WT patients with high FLT3 expression, which we did not observe with CD135 expression as determined by MFI. (28) It is important to note that in a smaller subset of patients with mRNA FLT3 transcript expression we did observe among FLT3 /ITD-negative patients a significantly lower EFS and corresponding increased RR, although there was no difference in OS.…”

Section: Discussionsupporting

confidence: 93%

Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Tarlock

Alonzo

Loken

et al. 2017

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose The FLT3 cell-surface receptor tyrosine kinase (CD135) is expressed in a majority of both acute lymphoid leukemia (ALL) and myeloid leukemia (AML). However, the prognostic significance of CD135 expression in AML remains unclear. We therefore evaluated the association between FLT3 surface expression and disease characteristics and outcomes in pediatric patients with AML. Experimental Design We analyzed FLT3 receptor expression on AML blasts by multi-dimensional flow cytometry and its association with disease characteristics, clinical outcomes, and FLT3 transcript level in 367 children with AML treated on the Children’s Oncology Group trial AAML0531. Results There was high variability in blast CD135 cell-surface expression across specimens. CD135 expression measure by flow cytometry was not correlated with FLT3 transcript expression determined by quantitative RT-PCR. Overall, CD135 expression was not significantly different for patients with FLT3/WT and those with FLT3/ITD and FLT3/ALM (p=0.25). High cell-surface CD135 expression was associated with FAB M5 subtype (p<0.001), KMT2A rearrangements (p=0.009) and inversely associated with inv(16)/t(16;16) (p< 0.001). Complete remission rate, overall survival, disease-free survival, and relapse rates were not significantly different between patients with low and high CD135 expression. Conclusions FLT3 cell-surface expression did not vary by FLT3 mutational status, but high FLT3 expression was strongly associated with KMT2A rearrangements. Our study found that there was no prognostic significance of FLT3 expression in pediatric AML.

show abstract

Section: Discussionsupporting

confidence: 93%

Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Tarlock

Alonzo

Loken

et al. 2017

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Furthermore, high expression of wt FLT3 has been suggested to be associated with both distinct AML subtypes and an unfavorable prognosis in both adult and pediatric AML. [8][9][10] Mutations in the nucleophosmin gene (NPM1, 5q35) and in the CCAAT/enhancer binding protein, ␣ gene (CEBPA, 19q13) have been identified in patients with AML. 11,12 AML with mutated NPM1 or mutated CEBPA is associated with a favorable prognosis, [13][14][15][16] and these have been defined as provisionally distinct entities in the 2008 World Health Organization classification of AML.…”

Section: Introductionmentioning

confidence: 99%

Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia

Staffas

Kanduri

Hovland

et al. 2011

Blood

View full text Add to dashboard Cite

“…Many clinical features such as favorable cytogenetics (eg, t[15;17], inv[16], and t[8;21] [1–3]) and a good initial treatment response are associated with a good outcome 4. However, the diagnosis encompasses a very heterogeneous group of leukemias with distinct response to chemotherapy 5. The clinical outcome of pediatric AML patients with similar treatment response varies greatly.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia

Bai¹,

Guo²,

Zhang³

et al. 2012

OTT

View full text Add to dashboard Cite

Objective:MicroRNA-100 (miR-100), a small noncoding RNA molecule, acts as a tumor suppressor or an oncogene in different cancers. The aberrant expression of this microRNA has been demonstrated as a frequent event in adult patients with acute myeloid leukemia (AML), but little is known for pediatric AML. The aim of this study was to investigate the expression and clinical significance of miR-100 in pediatric AML.Methods:The expression levels of miR-100 in bone marrow mononuclear cells were detected by real-time quantitative polymerase chain reaction in a cohort of 106 patients with de novo pediatric AML. The prognostic values of miR-100 in pediatric AML were also analyzed.Results:Compared with normal controls, upregulation of miR-100 in the bone marrow of pediatric AML patients with statistically significant differences (P < 0.001) was found. The expression levels of miR-100 were found to be significantly higher in pediatric AML patients with extramedullary disease, with the French–American–British classification subtype M7, and with unfavorable day 7 response to induction chemotherapy (P = 0.008, 0.001 and 0.01, respectively). Moreover, both univariate and multivariate analyses revealed that miR-100 upregulation was associated with poorer relapse-free and overall survival in pediatric AML patients.Conclusion:This is the first report demonstrating the upregulation of miR-100 in pediatric AML, and its association with poor relapse-free and overall survival. These results suggest that miR-100 upregulation may be used as an unfavorable prognostic marker in pediatric AML.

show abstract

High Transcript Level of FLT3 Associated with High Risk of Relapse in Pediatric Acute Myeloid Leukemia

Cited by 17 publications

References 28 publications

Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Disease Characteristics and Prognostic Implications of Cell-Surface FLT3 Receptor (CD135) Expression in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia

Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia

Contact Info

Product

Resources

About