Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population‐based study from the Swedish AML registry

Lazarevic, Vladimir; Rosso, Aldana; Juliusson, Gunnar; Antunović, Petar; Derolf, Åsa Rangert; Deneberg, Stefan; Möllgård, Lars; Uggla, Bertil; Wennström, Lovisa; Wåhlin, Anders; Höglund, Martin; Lehmann, Sören; Johansson, Bertil

doi:10.1111/ejh.12861

Cited by 16 publications

(12 citation statements)

References 45 publications

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“…Although trisomy 8 is classified as intermediate risk AML in most risk stratification systems, initial remission rates after 7 + 3 induction therapy are reported to be around 50-70% which is slightly lower than in the average patient population with approximately 80% [7,32,34,35]. Matching these reports, in our analysis, patients with a trisomy 8 more often had to be transplanted with active disease.…”

Section: Discussionsupporting

confidence: 63%

Risk Stratification, Measurable Residual Disease, and Outcomes of AML Patients with a Trisomy 8 Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Backhaus

Jentzsch

Bischof

et al. 2021

Cancers

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Background: For most patients with acute myeloid leukemia (AML) harboring a trisomy 8 an allogeneic hematopoietic stem cell transplantation (HSCT) is a suitable and recommended consolidation therapy. However, comparative outcome analyses between patients with and without trisomy 8 undergoing allogeneic HSCT have not been performed so far. Methods: We retrospectively analyzed clinical features, outcomes, and measurable residual disease (MRD) of 659 AML (12%, n = 81, with a trisomy 8) patients subjected to allogeneic HSCT as a consolidation therapy. Results: The presence of a trisomy 8 associated with a trend for higher age at diagnosis, AML of secondary origin, lower white blood cell counts at diagnosis, worse ELN2017 genetic risk, wild-type NPM1, and mutated IDH1/2 and JAK2. Outcomes after allogeneic HSCT in the entire cohort did not differ between patients with a sole trisomy 8, trisomy 8 with additional cytogenetic aberrations or without a trisomy 8. A trisomy 8 did not affect outcomes within the three ELN2017 risk groups. In accordance with findings in unselected patient cohorts, persistent MRD at allogeneic HSCT in patients with a trisomy 8 identified individuals with a higher risk of relapse following allogeneic HSCT. Conclusions: Outcomes of trisomy 8 patients after allogeneic HSCT did not compare unfavorably to that of other AML patients following allogeneic HSCT. Rather than the presence or absence of a trisomy 8, additional genetic aberrations and MRD at HSCT define outcome differences and aid in informed treatment decisions.

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Section: Discussionsupporting

confidence: 63%

Risk Stratification, Measurable Residual Disease, and Outcomes of AML Patients with a Trisomy 8 Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Backhaus

Jentzsch

Bischof

et al. 2021

Cancers

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“…Recurrent chromosomal abnormalities are identified in 55-60% of newly diagnosed adults with AML and provide powerful prognostic information [1][2][3]. The acquisition of an additional, third copy, of an intact chromosome (trisomy) occurs as a sole abnormality in 7-8% of adult patients with AML [4,5]. However, the molecular features of AML patients with these numerical abnormalities are not well understood.…”

Section: Introductionmentioning

confidence: 99%

“…Among sole trisomies, those involving chromosomes 4, 8, 11, 13 and 21 account for 89-95% of all sole trisomies in AML patients [4,5], and each associates with variable disease outcomes [4][5][6][7][8][9][10][11]. For instance, patients with sole trisomy 8 (+8), the most frequently detected trisomy, have been reported to have an intermediate outcome according to some [2], and an adverse outcome according to other studies [9].…”

Section: Introductionmentioning

confidence: 99%

“…For instance, patients with sole trisomy 8 (+8), the most frequently detected trisomy, have been reported to have an intermediate outcome according to some [2], and an adverse outcome according to other studies [9]. AML patients with isolated +4, +11, + 13 and +21 had a poor prognosis in most [4,7,[10][11][12], but not all [5], reports. Patients with any sole trisomy are categorized as having intermediate-risk disease according to the 2017 European LeukemiaNet (ELN) classification, provided that no other coexisting gene mutations lead to their reclassification into the favorable-or adverse-risk groups [13].…”

Section: Introductionmentioning

confidence: 99%

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Clinical and molecular characterization of patients with acute myeloid leukemia and sole trisomies of chromosomes 4, 8, 11, 13 or 21

et al. 2019

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Sole trisomies of chromosomes 4, 8, 11, 13 and 21 account for 89-95% of all sole trisomies in adult AML patients. We analyzed clinical and molecular characteristics of 138 de novo AML patients with sole +4, +8, +11, +13 or +21, and compared them with AML patients with those trisomies occurring in addition to other chromosome abnormalities (non-sole trisomy) and with cytogenetically normal AML (CN-AML) patients. Mutations in methylation-related genes were most commonly observed within each sole trisomy group (+4, 55%; +8, 58%; +11, 71%; +13, 71%; +21, 75% of patients). Patients with sole trisomies, excluding +4, also had frequent mutations in spliceosome genes (+8, 43%; +11, 65%; +13, 65%; +21, 45% of patients). In contrast, +4 patients frequently had mutations in transcription factor genes (44%) and NPM1

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“…The genetic and molecular consequences of trisomy 4 are, in general, unknown (3,4,7,8). Possible mechanisms involve global gene expression alterations because of gene dosage effects, including duplication of rearranged or mutated genes on chromosome 4.…”

Section: Discussionmentioning

confidence: 99%

Molecular Genetic Characterization of Acute Myeloid Leukemia With Trisomy 4 as the Sole Chromosome Abnormality

Torkildsen

Gorunova

Heim

et al. 2019

Cancer Genomics Proteomics

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Background/Aim: The aim of the study was to determine the genetic and molecular consequences of trisomy 4, a recurrent but rare chromosomal abnormality in acute myeloid leukemia (AML). Materials and Methods: Interphase fluorescence in situ hybridization, reverse transcriptasequantitative polymerase chain reaction for 28 chromosomal gene translocations/fusion genes, and targeted sequencing analyses were performed on five AMLs with trisomy 4 as the sole chromosomal anomaly. Results: An NPM1 frameshift mutation was found in all leukemic bone marrows, DNMT3A, FLT3, and IDH1 mutations were found in three, KIT and NRAS mutations in two, whereas IDH2 (R140Q), RUNX1, and WT1 mutations were found in only one patient each. The three patients with a DNMT3A (R882H) mutation have died. In contrast, the two patients whose leukemic cells were without this mutation, are alive 55 and 31 months after diagnosis, respectively. Conclusion: The results suggest a possible association between trisomy 4 and additional mutations that may influence prognosis. Acute myeloid leukemia (AML) is a heterogenous group of malignancies with different clinical phenotypes and responses to therapy (1, 2). AMLs can be classified according to distinct cytogenetic and genetic abnormalities of leukemic cells at diagnosis, but also by phenotypic and epigenetic differences that act as a guide to risk assessment and choice of treatment (1, 2). AML cases with a single trisomy constitute a heterogenous subgroup with regard to clinical, morphological, and immunophenotypic features, as well as the mutational profiles (3). Trisomy 4 is a recurrent, but rare chromosomal abnormality in AML. It may be the sole aberration or one of several chromosomal changes (4). Trisomy 4 was first described by Mecucci et al. in 1986, and a year later by Sandberg et al. (5), as the sole chromosomal abnormality in AML (6). In the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, 83 (48 female and 35 male patients) out of 18029 AML-cases had trisomy 4 as the sole chromosomal abnormality (http://cgap.nci.nih.gov/Chromosomes/Mitelman, database last updated on February 20, 2017). Most cases are morphologically classified as M1, M2, or M4 using the French-American-British (FAB) classification. Because trisomy 4 is rare, few studies have addressed its clinical impact. As a consequence, the prognosis of AML with solitary trisomy 4 remains unclear (7, 8). However, a recent study based on 87 AML cases with trisomy 4 concluded that the prognostic significance of the aberration depended on the patient's age, and despite an initial good response to treatment, patients with trisomy 4 were prone to relapse (4). Recently, we reported the genetic, molecular and clinical features of a pediatric AML case with trisomy 4 and an FLT3-ITD mutation (9). Fluorescence in situ hybridization assay demonstrated that part of the RUNX1 probe had moved to chromosome band 6q25 indicating a cryptic t(6;21)(q25;q22) translocation. Molecular analysis of the translocation showed fusion of RUNX1 w...

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Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population‐based study from the Swedish AML registry

Abstract: AML with single trisomies, with the exception of +13, should be grouped as IR.

Cited by 16 publications

References 45 publications

Risk Stratification, Measurable Residual Disease, and Outcomes of AML Patients with a Trisomy 8 Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Risk Stratification, Measurable Residual Disease, and Outcomes of AML Patients with a Trisomy 8 Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Clinical and molecular characterization of patients with acute myeloid leukemia and sole trisomies of chromosomes 4, 8, 11, 13 or 21

Molecular Genetic Characterization of Acute Myeloid Leukemia With Trisomy 4 as the Sole Chromosome Abnormality

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