The genotype nucleophosmin mutated and FLT3-ITD negative is characterized by high bax/bcl-2 ratio and favourable outcome in acute myeloid leukaemia.
Nucleophosmin gene (NPM1) mutations characterize acute myeloid leukaemia (AML) with normal karyotype and frequently co-exist with FLT3 internal tandem duplications (ITD). We evaluated bcl-2, bax, NPM1 and FLT3-ITD in 222 AML patients. Bax/bcl-2 ratio >0.35 and NPM1 without FLT3-ITD were significantly associated (P = 0.0001). NPM1-mutated (mt)/FLT3-ITD negative patients showed a higher complete remission (CR) rate (90%, P = 0.0002) and a longer overall survival (OS, P = 0.00007). NPM1-mt/FLT3-ITD negative plus bax/bcl-2 > 0.35 subset showed a very high CR rate (96%), very long OS (P = 0.00005) and disease-free survival (P = 0.004). The favourable prognosis of NPM1-mt/FLT3-ITD negative patients might be explained by a higher bax/bcl-2 ratio.
Del Poeta
Giovanni
G
Department of Haematology, Ospedale S.Eugenio, University Tor Vergata, Rome, Italy. g.delpoeta@tin.it
Ammatuna
Emanuele
E
Lavorgna
Serena
S
Capelli
Giovanni
G
Zaza
Serena
S
Luciano
Fabrizio
F
Ottone
Tiziana
T
Del Principe
Maria Ilaria
MI
Buccisano
Francesco
F
Maurillo
Luca
L
Panetta
Paola
P
de Fabritiis
Paolo
P
Stasi
Roberto
R
Venditti
Adriano
A
Amadori
Sergio
S
Lo Coco
Francesco
F
D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D020080:Tandem Repeat Sequences / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C494826:BAX protein, human; D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3