High Id1 expression is associated with poor prognosis in 237 patients with acute myeloid leukemia.
Inhibitors of differentiation (Id) are a group of dominant inhibitors of basic helix-loop-helix transcriptional factors, which promote excessive proliferation, and also protect cells against drug-induced apoptosis in mammalians. Recently, Id1 has been identified as a common downstream target of several constitutively activated oncogenic tyrosine kinase, such as FLT3 internal tandem duplication, in leukemia cells. We analyzed Id1 expression as possible prognostic factor in 237 acute myeloid leukemia (AML) patients. High Id1 expression was associated with older age (P = .009) and with FLT3 internal tandem duplication (P = .003). However, 61% of the patients in the group of FLT3(-) AML were Id1(+), suggesting that other tyrosine kinases are involved. In whole population, high Id1 expression independently predicted shorter disease-free survival (P = .05) and overall survival (P = .003). In young patients (age <OR= 60 years) with normal cytogenetics, Id1(+) was, in multivariate analysis, associated with lower complete remission rates (P = .02), shorter disease-free survival (P = .02), and overall survival (P = .006). In conclusion, our data provide a new molecular marker for refining the risk classification of AML, especially in young patients with normal cytogenetic. Id1(-) patients with normal cytogenetic should be classified as favorable-risk leukemia. Id1, as a downstream target of constitutively activated tyrosine kinase, could be a suitable candidate for targeted therapy.
Tang
Ruoping
R
Département d'Hématologie, Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, Paris, France.
Hirsch
Pierre
P
Fava
Fanny
F
Lapusan
Simona
S
Marzac
Christophe
C
Teyssandier
Irène
I
Pardo
Julia
J
Marie
Jean-Pierre
JP
Legrand
Ollivier
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000090243:Nucleophosmin; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D020080:Tandem Repeat Sequences / Q000235:genetics; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism
C442828:BAALC protein, human; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3