Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value.
Somatic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) were recently demonstrated in acute myeloid leukemia (AML), but their prevalence and prognostic impact remain to be explored in large extensively characterized AML series, and also in various other hematologic malignancies. Here, we demonstrate in 893 newly diagnosed cases of AML mutations in the IDH1 (6%) and IDH2 (11%) genes. Moreover, we identified IDH mutations in 2 JAK2 V617F myeloproliferative neoplasias (n = 96), a single case of acute lymphoblastic leukemia (n = 96), and none in chronic myeloid leukemias (n = 81). In AML, IDH1 and IDH2 mutations are more common among AML with normal karyotype and NPM1(mutant) genotypes. IDH1 mutation status is an unfavorable prognostic factor as regards survival in a composite genotypic subset lacking FLT3(ITD) and NPM1(mutant). Thus, IDH1 and IDH2 mutations are common genetic aberrations in AML, and IDH1 mutations may carry prognostic value in distinct subtypes of AML.
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Saman
S
Abbas
Sanne
S
Lugthart
François G
FG
Kavelaars
Anita
A
Schelen
Jasper E
JE
Koenders
Annelieke
A
Zeilemaker
Wim J L
WJ
van Putten
Anita W
AW
Rijneveld
Bob
B
Löwenberg
Peter J M
PJ
Valk
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006402:Hematologic Diseases; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053614:Janus Kinase 2 / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D015995:Prevalence; D011379:Prognosis; D055815:Young Adult
C000716967:NPM1 protein, human; D000090243:Nucleophosmin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D053614:Janus Kinase 2