Prognostički značaj mutacija u genima za izocitrat dehidrogenazu 1 (IDH1) i izocitrat dehidrogenazu 2 (IDH2) u akutnoj mijeloidnoj leukemiji sa normalnim kariotipom
Prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations on outcome in acute myeloid leukemia with normal karyotype
Author
Virijević, Marijana M.Mentor
Tomin, DragicaCommittee members
Mihaljević, Biljana
Suvajdžić-Vuković, Nada

Đurđević, Predrag

Metadata
Show full item recordAbstract
Mutacije u genima za izocitrat dehidrogenazu 1 i 2 (IDH1 i IDH2) su česte rekurentne
molekularne promene kod akutne mijeloidne leukemije sa normalnim kariotipom (AMLNK).
Uticaj IDH mutacija na kliničke karakteristike i ishod lečenja kod AML-NK su u
velikoj meri istražene, ali samo nekoliko studija je pratilo ove mutacije u toku bolesti.
Ciljevi: 1) Utvrđivanje učestalosti prisustva IDH1 i IDH2 mutacija kod bolesnika sa AMLNK;
2) Utvrđivanje uticaja prisustva IDH1 i IDH2 mutacija na učestalost i dužinu remisije,
ukupno preživljavanje i povezanosti IDH1 i IDH2 mutacija i drugih prognostičkih markera:
parametri krvne slike, biohemijski parametri, citološki tip bolesti, imunofenotipska i
molekularno-genetska obeležja (FLT3 i NPM1 mutacije); 3) Utvrđivanje stabilnosti IDH1 i
IDH2 mutacija u toku bolesti poređenjem uzoraka na početku bolesti sa uzorcima u toku
kompletne remisije (KR), odnosno u recidivu bolesti.
Materijal i metodologija istraživanja: Uzorci od 110 starijih de novo AML-NK bol...esnika
bili su ispitani na IDH1 i IDH2 mutaciju. Ispitana je njihova povezanost sa drugim
prognostičkim markerima i ishodom lečenja. Pored toga, praćena je stabilnost ovih mutacija
u KR i recidivu.
Rezultati: IDH mutacije su nađene kod 25 (23%) bolesnika: IDH1 je imalo 8 (7%) bolesnika,
svi od njih su imali IDHR132; IDH2 je imalo 17 (16%) bolesnika (15 IDHR140; 2 IDHR172).
IDH+ bolesnici su imali viši broj trombocita (p=0.024), kao i veći procenat blasta u perifernoj
krvi (p=0.031) u odnosu na IDH- bolesnike. IDH+ bolesnici su imali nižu stopu KR u
poređenju sa IDH- bolesnicima (44% vs 60%, p=0.152), ali to nije bilo statistički značajno.
Osim toga, IDH mutacije su imale samo neznatan uticaj na trajanje remisije bez bolesti
(IDH+-12 meseci vs IDH--17 meseci; p=0.091), dok je ukupno preživljavanje (OS) IDH+
bolesnika bilo kraće u poređenju sa IDH- bolesnicima (2 vs 7 meseci; p=0.039). Nepovoljan
uticaj IDH mutacije na OS je naročito bio očigledan kod bolesnika koji nisu imali NPM1
mutaciju (5 vs 12 meseci, p=0.050). IDH mutacije su ispitivane sekvencionalno kod 19 IDH+
bolesnika koji su bili živi posle indukcije...
Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are
frequent recurrent molecular lesions in acute myeloid leukemia with normal karyotype
(AML-NK). The effects of IDH mutations on clinical features and treatment outcome in
AML-NK have been widely investigated, but only a few studies monitored these mutations
during follow-up.
Aim: 1) To determine the frequency of presence of IDH1 and IDH2 mutations in patients
with AML-NK; 2) To determine the effect of the presence of IDH1 and IDH2 mutations on
duration of remission, overall survival and the association IDH1 and IDH2 mutations and
other prognostic markers: blood parameters, the biochemical parameters, cytological disease
type, immunophenotypic and molecular-genetic characteristics (FLT3 and NPM1 mutations);
3) To determine the stability IDH1 and IDH2 mutations in the course of the disease by
comparing the samples at the start of the disease with samples during complete remission
(CR), and in a relapse of the dise...ase.
Material and methodes: Samples from 110 adult de novo AML-NK patients were assessed
for IDH1 and IDH2 mutations. Their association with other prognostic markers and outcome
was analyzed. In addition, we monitored the stability of these mutations during CR and
relapse.
Results: IDH mutations were found in 25 (23%) patients: IDH1 in 8 (7%), all of them
IDHR132; IDH2 in 17 (16%) patients (15 IDHR140; 2 IDHR172). IDH+ patients had higher
platelet counts (p=0.024), as well as a higher percentage of peripheral blood blasts (p=0.031)
than IDH- patients. They tended to have a lower CR rate compared to IDH- patients (44% vs
60%, p=0.152), but this was not statistically significant. Moreover, IDH mutations had only
a slight impact on disease free survival (IDH+-12 months vs IDH--17 months; p=0.091), but
overall survival (OS) of our IDH+ patients was shorter in comparison with IDH- patients (2
vs 7 months; p=0.039)...