Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10324733" target="_blank" >RIV/00064203:_____/16:10324733 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/16:10324733

Výsledek na webu

<a href="http://dx.doi.org/10.1182/blood-2016-01-695551" target="_blank" >http://dx.doi.org/10.1182/blood-2016-01-695551</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1182/blood-2016-01-695551" target="_blank" >10.1182/blood-2016-01-695551</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study

Popis výsledku v původním jazyce

Genetic abnormalities and early treatment response are the main prognostic factors in acute myeloid leukemia (AML). Acute megakaryoblastic leukemia (AMKL) is a rare subtype of AML. Deep sequencing has identified CBFA2T3/GLIS2 and NUP98/KDM5A as recurrent aberrations, occurring in similar frequencies as RBM15/MKL1 and KMT2A-rearrangements. We studied whether these cytogenetic aberrations can be used for risk group stratification. To assess frequencies and outcome parameters of recurrent cytogenetic aberrations in AMKL, samples and clinical data of patients treated by the Associazione Italiana Ematologia Oncologia Pediatrica, Berlin-Frankfurt-Munster Study Group, Children's Oncology Group, Dutch Childhood Oncology Group, and the Saint Louis Hopital were collected, enabling us to screen 153 newly diagnosed pediatric AMKL cases for the aforementioned aberrations and to study their clinical characteristics and outcome. CBFA2T3/GLIS2 was identified in 16% of the cases; RBM15/MKL1, in 12%; NUP98/KDM5A and KMT2A rearrangements, in 9% each; and monosomy 7, in 6%. These aberrations were mutually exclusive. RBM15/MKL1-rearranged patients were significantly younger. No significant differences in sex and white blood cell count were found. NUP98/KDM5A, CBFA2T3/GLIS2, KMT2A-rearranged lesions and monosomy 7 (NCK-7) independently predicted a poor outcome, compared with RBM15/MKL1-rearranged patients and those with AMKL not carrying these molecular lesions. NCK-7-patients (n=61) showed a 4-year probability of overall survival of 35 6 6% vs 70 +/- 5% in the RBM15/MKL1-other groups (n = 92, P<.0001) and 4-year probability of event-free survival of 33 +/- 6% vs 62 +/- 5% (P=.0013), the 4-year cumulative incidence of relapse being 42 +/- 7% and 19 +/- 4% (P=.003), respectively. We conclude that these genetic aberrations may be used for risk group stratification of pediatric AMKL and for treatment tailoring.

Název v anglickém jazyce

Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study

Popis výsledku anglicky

Genetic abnormalities and early treatment response are the main prognostic factors in acute myeloid leukemia (AML). Acute megakaryoblastic leukemia (AMKL) is a rare subtype of AML. Deep sequencing has identified CBFA2T3/GLIS2 and NUP98/KDM5A as recurrent aberrations, occurring in similar frequencies as RBM15/MKL1 and KMT2A-rearrangements. We studied whether these cytogenetic aberrations can be used for risk group stratification. To assess frequencies and outcome parameters of recurrent cytogenetic aberrations in AMKL, samples and clinical data of patients treated by the Associazione Italiana Ematologia Oncologia Pediatrica, Berlin-Frankfurt-Munster Study Group, Children's Oncology Group, Dutch Childhood Oncology Group, and the Saint Louis Hopital were collected, enabling us to screen 153 newly diagnosed pediatric AMKL cases for the aforementioned aberrations and to study their clinical characteristics and outcome. CBFA2T3/GLIS2 was identified in 16% of the cases; RBM15/MKL1, in 12%; NUP98/KDM5A and KMT2A rearrangements, in 9% each; and monosomy 7, in 6%. These aberrations were mutually exclusive. RBM15/MKL1-rearranged patients were significantly younger. No significant differences in sex and white blood cell count were found. NUP98/KDM5A, CBFA2T3/GLIS2, KMT2A-rearranged lesions and monosomy 7 (NCK-7) independently predicted a poor outcome, compared with RBM15/MKL1-rearranged patients and those with AMKL not carrying these molecular lesions. NCK-7-patients (n=61) showed a 4-year probability of overall survival of 35 6 6% vs 70 +/- 5% in the RBM15/MKL1-other groups (n = 92, P<.0001) and 4-year probability of event-free survival of 33 +/- 6% vs 62 +/- 5% (P=.0013), the 4-year cumulative incidence of relapse being 42 +/- 7% and 19 +/- 4% (P=.003), respectively. We conclude that these genetic aberrations may be used for risk group stratification of pediatric AMKL and for treatment tailoring.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

—

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Blood

ISSN

0006-4971

e-ISSN

—

Svazek periodika

127

Číslo periodika v rámci svazku

26

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

3424-3430

Kód UT WoS článku

000379248500018

EID výsledku v databázi Scopus

2-s2.0-84977278887