Recurrent genetic abnormalities can be used for risk-group stratification in pediatric AMKL: results of a retrospective intergroup study.

Publication Type:

Journal Article


Blood (2016)


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 AIEOP, BFM-SG, COG, DCOG 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 was identified 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 to RBM15/MKL1-rearranged patients and to those with AMKL not carrying these molecular lesions. NCK-7-patients (n=61) showed a 4-yr pOS of 35±6% vs 70±5% in the RBM15/MKL1-other groups (n=92, p<0.0001), and 4-yr pEFS of 33±6% vs 62±5% (p=0.0013), the 4-yr cumulative incidence of relapse being 42±7% and 19±4% (p=0.003), respectively. We conclude that these genetic aberrations may be used for risk-group stratification of pediatric AMKL and for treatment tailoring.