The prognosis predictive value of FMS-like tyrosine kinase 3-internal tandem duplications mutant allelic ratio (FLT3-ITD MR) in patients with acute myeloid leukemia detected by GeneScan.

Abstract

INTRODUCTION:

This study aimed to explore the significance and cut-off values of FMS-like tyrosine kinase 3-internal tandem duplications mutant allelic ratio (FLT3-ITD MR) in prognostic evaluation of acute myeloid leukemia (AML) patients.

METHODS:

This study enrolled 249 Chinese AML patients. The exons 14 and 15 of FLT3 gene were amplified by genomic polymerase chain reaction. GeneScan and single nucleotide sequencing were also performed. Participants were grouped into high- and low-ratio FLT3-ITD MR (FLT3-ITD MRhigh and FLT3-ITD MRlow) applying the median of FLT3-ITD MR as the cut-off ratio, and patients without FLT3-ITD were grouped as FLT3-wild type (wt). Duration of complete remission (CR), relapsed remission and overall survival (OS) were examined.

RESULTS:

FLT3-ITD was detected in 58 patients. The medians of FLT3-ITD MR were 0.31 and 0.29 for all AML and non-M3 patients, respectively. For all patients, FLT3-ITD MRhigh group had the lowest CR rate among these 3 groups (p < 0.001). The FLT3-wt group, FLT3-ITD MRlow and FLT3-ITD MRhigh group had the median OS of 36.00 months (range: 2.00-92.00 months), 12.00 months (range: 1.00-78.00 months) and 14.00 months (range: 0.00-79.00 months), respectively. Subjects in FLT3-ITD MRhigh group had 2.675 times (95% CI: 1.726-4.146; p < 0.001) and 1.879 times (95% CI: 1.061-3.328; p = 0.031) higher death risk than those in FLT3-wt group and FLT3-ITD MRlow group, respectively. For non-M3 patients, the median OS was 35.00 months (range: 2.00-92.00 months), 9.5 months (range: 1.00-74.00 months) and 10.00 months (range: 1.00-38.00 months) in the FLT3-wt group, FLT3-ITD MRlow group and FLT3-ITD MRhigh group, respectively. Non-M3 patients in FLT3-ITD MRhigh group had 3.301 times (95% CI: 1.423-7.661; p = 0.005) higher death risk than those in FLT3-wt group.

CONCLUSION:

The present study found that FLT3-ITD MR is closely related to CR and OS in AML patients. Furthermore, FLT3-ITD MR may serve as an independent prognostic factor for OS in non-M3 AML patients. Classifying risk grades based on FLT3-ITD MR is crucial for individualized treatment and prognostic evaluation.

• Authors: Mengyuan Lyu, Hongyan Liao, Xiao Shuai, Yongmei Jin, Jun Su, Qin Zheng
• Journal: Gene (Gene) Vol. 726 Pg. 144195 (Feb 05 2020) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 31669649 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• FLT3 protein, human
• fms-Like Tyrosine Kinase 3

Topics

• Adult
• Alleles
• Exons (genetics)
• Female
• Humans
• Leukemia, Myeloid, Acute (genetics, pathology)
• Male
• Middle Aged
• Mutation (genetics)
• Prognosis
• Tandem Repeat Sequences (genetics)
• fms-Like Tyrosine Kinase 3 (genetics)