Hyperdiploid karyotypes in acute myeloid leukemia define a novel entity: a study of 38 patients from the Groupe Francophone de Cytogenetique Hematologique (GFCH)

Luquet, Isabelle; Laı̈, Jean-Luc; Barin, Carole; Baranger, Laurence; Bilhou-Nabéra, Chrystèle; Lippert, Éric; Gervais, Carine; Talmant, Pascaline; Cornillet‐Lefèbvre, Pascale; Pérot, Christine; Nadal, Nathalie; Mozziconacci, Marie‐Joëlle; Lafage‐Pochitaloff, Marina; Éclache, Virginie; Mugneret, Francine; Lefebvre, Catherine Lemieux; Herens, Christian; Speleman, Franki; Poirel, Hélène; Tigaud, Isabelle; Cabrol, C; Rousselot, Philippe; Daliphard, Sylvie; Imbert, M; Garand, Richard; Geneviève, Franck; Berger, Roland; Terré, Christine

doi:10.1038/sj.leu.2404974

Cited by 28 publications

(38 citation statements)

References 18 publications

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“…26,27 In adult and pediatric AML hyperdiploidy was reported to result in intermediate or poor outcome, and other studies showed that hyperdiploid cases should be assessed for the presence of specific abnormalities to predict outcome. 26,29,30 Based on our results a hyperdiploid karyotype should not be considered as risk factor in pediatric AMKL.…”

Section: Discussionmentioning

confidence: 67%

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

Rooij

Masetti

Heuvel‐Eibrink

et al. 2016

Blood

160

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Key Points• NUP98/KDM5A, CBFA2T3/ GLIS2, KMT2A-rearrangements, and monosomy 7 are associated with poor outcome; RBM15/ MKL1 and others fare better.• Screening for NUP98/ KDM5A, RBM15/MKL1, CBFA2T3/GLIS2, and KMT2A rearrangements combined with conventional karyotyping is advisable.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 5 61) showed a 4-year probability of overall survival of 35 6 6% vs 70 6 5% in the RBM15/MKL1-other groups (n 5 92, P < .0001) and 4-year probability of event-free survival of 33 6 6% vs 62 6 5% (P 5 .0013), the 4-year cumulative incidence of relapse being 42 6 7% and 19 6 4% (P 5 .003), respectively. We conclude that these genetic aberrations may be used for risk group stratification of pediatric AMKL and for treatment tailoring. (Blood. 2016;127(26):3424-3430)

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Section: Discussionmentioning

confidence: 67%

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

Rooij

Masetti

Heuvel‐Eibrink

et al. 2016

Blood

160

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“…In general, HH and tetraploidy appears infrequently in AML; it seen primarily in de novo disease in older male patients (> 60 years) with low remission rates and short overall survival (OS) [9, 10]. Unfortunately only limited data on incidence and clinical implications of HH and tetraploidy in AML is available.…”

Section: Discussionmentioning

confidence: 99%

“…≥49 chromosomes with or without additional structural rearrangements) is a very rare event observed in small subset of adult AML (< 2%) only [9, 10]; it is primarily seen in de novo AML and older male patients with low remission rate and short survival [9]. Interestingly, Chilton et al [11] indicated that not all HH-AML patients should be automatically classified as having adverse prognosis.…”

Section: Introductionmentioning

confidence: 99%

A new adult AML case with an extremely complex karyotype, remission and relapse combined with high hyperdiploidy of a normal chromosome set in secondary AML

et al. 2018

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BackgroundChromosomal abnormalities are diagnostic and prognostic key factors in acute myeloid leukemia (AML) patients, as they play a central role for risk stratification algorithms. High hyperdiploidy (HH), a rare cytogenetic abnormality seen commonly in elder male AML patients, is normally categorized under AML with complex karyotype (CK). Accordingly, patients with HH generally are associated with low remission rates and a short overall survival.Case presentationHere we report a case of 21-year-old female, diagnosed with a de novo AML-M1 according to WHO classification and a CK at diagnosis. Cytogenetic, molecular cytogenetic approaches (standard fluorescence in situ hybridization (FISH), array-proven multicolor banding (aMCB)) and high resolution array comparative genomic hybridization (aCGH) analyses revealed a unique complex but still near diploid karyotype involving eleven chromosomes was identified. It included pentasomy 4, three yet unreported chromosomal aberrations t(1;2)(p35;p22), t(1;3)(p36.2;p26.2), and t(10;12)(p15.2;q24.11), and a combination of two cytogenetic events, yet unreported to appear in together, i.e. a reciprocal translocation t(1;3)(p36.2;p26.2) leading to EVI1/PRDM16 gene fusion, and monoallelic loss of tumor suppressor gene TP53. After successful chemotherapeutic treatment the patient experienced a relapse to AML-M1, and she developed secondary AML-M6 with tetraploidy and HH. Unfortunately, the young woman died 8.5 months after initial diagnosis.ConclusionsTo the best of our knowledge, a comparable adult AML associated with such a CK, coexistence of 3q rearrangements with loss of TP53 at diagnosis, and HH in secondary AML were not previously reported. Thus, the combination of the here seen chromosomal aberrations in adult primary AML seems to indicate for an adverse prognosis.

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“…Massive aneuploidy is not very common in AML and ALL; most cases display modal numbers close to the normal cellular content of 46 chromosomes [Mitelman et al, 2012]. In AML, only approximately 5% of the published cases have had modal numbers >50, and there is no evidence for CIN in AML in the literature [Iyer et al, 2004;Béné et al, 2006;Luquet et al, 2008;Mitelman et al, 2012]. Cases with <44 chromosomes constitute ∼ 3% of the published cases.…”

Section: Genomic Heterogeneity and Chromosomal Instability In Acute Lmentioning

confidence: 99%

Genomic Heterogeneity in Acute Leukemia

Paulsson¹

2013

Cytogenet Genome Res

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Acquired genetic aberrations are the underlying cause of leukemogenesis in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The karyotypes of AML and ALL cases are generally quite simple as seen by chromosome banding analysis, with few genetic changes and a limited number of subclones. However, investigations using fluorescence in situ hybridization, loss of heterozygosity analysis, single-nucleotide polymorphism arrays, and, most recently, massively parallel sequencing have challenged this view. In particular, comparison of diagnostic and relapse samples, modeling in transgenic mice, and whole-exome and whole-genome sequencing have indicated that widespread genomic heterogeneity, which is masked by a dominant clone, may be present in AML and ALL. In the present review, our current knowledge of genomic heterogeneity in acute leukemia is summarized.

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Hyperdiploid karyotypes in acute myeloid leukemia define a novel entity: a study of 38 patients from the Groupe Francophone de Cytogenetique Hematologique (GFCH)

Cited by 28 publications

References 18 publications

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

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

A new adult AML case with an extremely complex karyotype, remission and relapse combined with high hyperdiploidy of a normal chromosome set in secondary AML

Genomic Heterogeneity in Acute Leukemia

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