FLT3 mutations do not influence MDR-1 gene expression in acute myeloid leukemia.
BACKGROUND
A worse outcome for patients carrying FLT3 mutations or expressing MDR1 gene has been reported. This study was designed to verify the possible co-expression of mutated-FLT3 and MDR1 genes and to evaluate their independent prognostic role.


METHODS
Sixty-one AML patients were tested for MDR1-mRNA levels by real-time PCR and for FLT3 mutations by PCR and Genescan analysis.


RESULTS
FLT3 mutations were detected in 31% of patients, more frequently in patients < 60 years and at standard cytogenetic risk. Among 92% of patients MDR1-positive, 50% expressed high levels of mRNA. No significant correlation was found between FLT3 mutations and high levels of MDR1. FLT3 or MDR1 mutations failed to show any role concerning the CR achievement and OS. On the contrary, a significant disadvantage for DFS was found in the group of patients carrying FLT3/ITD.


CONCLUSIONS
The results reported above show that FLT3 mutations and MDR1 expression represent two independent clinical prognostic factors for AML patients.
Galimberti
Sara
S
Department of Oncology, Transplant and Advances in Medicine, Section of Hematology, University of Pisa, Italy.
Rossi
Angela
A
Palumbo
Giuseppe Alberto
GA
Morabito
Fortunato
F
Guerrini
Francesca
F
Vincelli
Iolanda
I
Fazzi
Rita
R
Santini
Valeria
V
Petrini
Mario
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D012074:Remission Induction; D012189:Retrospective Studies; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3