Quantification of VEGF isoforms and VEGFR transcripts by qRT-PCR and their significance in acute myeloid leukemia.
Vascular endothelial growth factor (VEGF) and its receptors are known to play an important role in normal and pathological hematopoiesis but the prognostic impact of VEGF isoform transcripts in acute myeloid leukemia (AML) has not been addressed. We conducted a single-institution prospective study to analyze the impact of these angiogenic factors and the expression of their receptors on the survival of adult patients newly diagnosed with AML. We investigated the levels of VEGF transcript isoforms VEGF121, -145, -165, -189 and -206 and their receptors, VEGFR-1 and VEGFR-2, using quantitative reverse transcriptase polymerase chain reaction assays in peripheral blood mononuclear cells (PBMCs) of 67 consecutive AML patients at diagnosis. VEGF total protein was measured for comparison with mRNA levels in PBMCs. The VEGF121 splice variant transcript in AML PBMCs was significantly higher than in the normal controls. VEGF transcripts were quantified in all samples while its protein was detected in 42/67 (63%) of AML samples. High levels of VEGF121, VEGF165 transcripts and VEGF protein in AML were significantly related to a worse prognosis when analyzing overall survival (p<0.0001, p=0.019 and p=0.012, respectively) or event-free survival (p<0.0001, p=0.010 and p=0.047) using univariate analysis. In multivariable analysis only VEGF121 expression remained an independent prognostic factor for either event-free survival or overall survival [aHR=8.83 (3.48-22.4), p<0.0001, and aHR=9.52 (3.41-26.6), p<0.0001]. No prognostic value was observed for the other isoforms and the two receptors. Our findings show that the level of VEGF121 mRNA in circulating cells from AML patients is a strong independent prognostic parameter, which could be useful in the management of unselected AML patients.
Mourah
Samia
S
INSERM U716, Laboratoire de Pharmacologie AP-HP, Hôpital Saint-Louis, Paris, France. samia.mourah@sls.aphp.fr
Porcher
Raphael
R
Lescaille
Géraldine
G
Rousselot
Philippe
P
Podgorniak
Marie-Pierre
MP
Labarchède
Géraldine
G
Naimi
Benyoussef
B
Medioni
Jacques
J
Dombret
Hervé
H
Calvo
Fabien
F
D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D007118:Immunoassay; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; D017931:DNA Primers; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2