Recurrent abnormalities can be used for risk group stratification in pediatric AMKL

A retrospective intergroup study

Jasmijn D E De Rooij, Riccardo Masetti, Marry M. Van Den Heuvel-Eibrink, Jean Michel Cayuela, Jan Trka, Dirk Reinhardt, Mareike Rasche, Edwin Sonneveld, Todd A. Alonzo, Maarten Fornerod, Martin Zimmermann, Martina Pigazzi, Rob Pieters, Soheil Meshinchi, C. Michel Zwaan, Franco Locatelli

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 Hôpital 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% 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.

Original languageEnglish
Pages (from-to)3424-3430
Number of pages7
JournalBlood
Volume127
Issue number26
DOIs
Publication statusPublished - Jun 30 2016

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Leukemia, Megakaryoblastic, Acute
Pediatrics
Aberrations
Retrospective Studies
Oncology
Acute Myeloid Leukemia
Chromosome Aberrations
High-Throughput Nucleotide Sequencing
Berlin
Leukocyte Count
Sex Characteristics
Disease-Free Survival
Blood
Recurrence
Cells
Survival
Incidence
Therapeutics
nuclear pore complex protein 98

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

De Rooij, J. D. E., Masetti, R., Van Den Heuvel-Eibrink, M. M., Cayuela, J. M., Trka, J., Reinhardt, D., ... Locatelli, F. (2016). Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: A retrospective intergroup study. Blood, 127(26), 3424-3430. https://doi.org/10.1182/blood-2016-01-695551

Recurrent abnormalities can be used for risk group stratification in pediatric AMKL : A retrospective intergroup study. / De Rooij, Jasmijn D E; Masetti, Riccardo; Van Den Heuvel-Eibrink, Marry M.; Cayuela, Jean Michel; Trka, Jan; Reinhardt, Dirk; Rasche, Mareike; Sonneveld, Edwin; Alonzo, Todd A.; Fornerod, Maarten; Zimmermann, Martin; Pigazzi, Martina; Pieters, Rob; Meshinchi, Soheil; Zwaan, C. Michel; Locatelli, Franco.

In: Blood, Vol. 127, No. 26, 30.06.2016, p. 3424-3430.

Research output: Contribution to journalArticle

De Rooij, JDE, Masetti, R, Van Den Heuvel-Eibrink, MM, Cayuela, JM, Trka, J, Reinhardt, D, Rasche, M, Sonneveld, E, Alonzo, TA, Fornerod, M, Zimmermann, M, Pigazzi, M, Pieters, R, Meshinchi, S, Zwaan, CM & Locatelli, F 2016, 'Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: A retrospective intergroup study', Blood, vol. 127, no. 26, pp. 3424-3430. https://doi.org/10.1182/blood-2016-01-695551
De Rooij JDE, Masetti R, Van Den Heuvel-Eibrink MM, Cayuela JM, Trka J, Reinhardt D et al. Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: A retrospective intergroup study. Blood. 2016 Jun 30;127(26):3424-3430. https://doi.org/10.1182/blood-2016-01-695551
De Rooij, Jasmijn D E ; Masetti, Riccardo ; Van Den Heuvel-Eibrink, Marry M. ; Cayuela, Jean Michel ; Trka, Jan ; Reinhardt, Dirk ; Rasche, Mareike ; Sonneveld, Edwin ; Alonzo, Todd A. ; Fornerod, Maarten ; Zimmermann, Martin ; Pigazzi, Martina ; Pieters, Rob ; Meshinchi, Soheil ; Zwaan, C. Michel ; Locatelli, Franco. / Recurrent abnormalities can be used for risk group stratification in pediatric AMKL : A retrospective intergroup study. In: Blood. 2016 ; Vol. 127, No. 26. pp. 3424-3430.
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AU - De Rooij, Jasmijn D E

AU - Masetti, Riccardo

AU - Van Den Heuvel-Eibrink, Marry M.

AU - Cayuela, Jean Michel

AU - Trka, Jan

AU - Reinhardt, Dirk

AU - Rasche, Mareike

AU - Sonneveld, Edwin

AU - Alonzo, Todd A.

AU - Fornerod, Maarten

AU - Zimmermann, Martin

AU - Pigazzi, Martina

AU - Pieters, Rob

AU - Meshinchi, Soheil

AU - Zwaan, C. Michel

AU - Locatelli, Franco

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N2 - 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 Hôpital 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% 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.

AB - 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 Hôpital 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% 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.

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