Trisomy 8 in acute myeloid leukemia

Hemsing, Anette Lodvir; Hovland, Randi; Tsykunova, Galina; Reikvam, Håkon

doi:10.1080/17474086.2019.1657400

Cited by 31 publications

(19 citation statements)

References 119 publications

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“…Trisomy 8 is often seen in the AML subgroup with transcription-factor-associated fusions CBFB-MYH11, RUNX1-RUNX1T1, and PML-RARA [30]. Notably, all five cases with MN1-ETV6 in this study were accompanied by trisomy 8, and genomic CNV analysis further revealed a shared 531 Kbps focal chr8 amplification in three of the other four cases.…”

Section: Discussionmentioning

confidence: 49%

Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12)

et al. 2020

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Chromosome translocation t(12;22)(p13;q12)/MN1-ETV6 and MN1 overexpression confer a subset of adverse prognostic AML but so far lack in-depth research. We focused on the clinical course and comprehensive genetic analysis of eight cases with t(12;22)(p13;q12) and one with t(12;17;22) (p13;q21;q13) to elucidate their molecular etiology and outcomes of allogeneic hemopoietic stem cell transplantation (allo-HSCT). The total incidence of t(12;22)(p13;q12) and related translocations was 0.32% in myeloid neoplasms. These patients were confirmed to have dismal prognosis when treated only with chemotherapy, and we firstly provided evidence that they can significantly benefit from timely allo-HSCT. Five cases were MN1-ETV6 positive, and a novel MN1-STAT3 fusion was identified in the patient with triadic translocation. Significant MN1 overexpression was observed in all three MN1-fusion-negative cases. Genetic analysis highlighted the evidence of an ectopic super-enhancer associated orchestrated mechanism of MN1 overexpression and ETV6 haploinsufficiency in t(12;22) (p13;q12) myeloid neoplasms, rather than the conventional thought of MN1-ETV6 fusion formation. We also disclosed the high concomitance of trisomy 8 and 531 Kbps focal 8q duplication in t(12;22)(p13;q12) cases. The new perspective about this entity of disease will enlighten further research to define the mechanism of tumorigenesis and discover effective treatments for MN1-driven malignancies.

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Section: Discussionmentioning

confidence: 49%

Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12)

et al. 2020

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“…Although trisomy 8 blasts have a specific signature, trisomy 8 AMLs are heterogeneous in terms of presence of additional molecular mutations [2]. Some of these molecular mutations might have a stronger prognostic impact than the trisomy 8 itself and might also influence the susceptibility of AML blasts to graft-versus-leukemia effects.…”

Section: Discussionmentioning

confidence: 99%

“…Trisomy 8 is one of the most frequent cytogenetic abnormality in acute myeloid leukemia (AML), occurring in 10-15% of AML patients and being the sole genetic abnormality in~5% of AML [1,2]. Although allogeneic hematopoietic stem cell transplantation (allo-HCT) has been frequently used in first complete remission (CR) in younger, fit AML patients with isolated trisomy 8 [3,4], there has been a paucity of data comparing allo-HCT to autologous hematopoietic stem cell transplantation (auto-HCT) or consolidation chemotherapy in these patients [2].…”

Section: Introductionmentioning

confidence: 99%

Better leukemia-free survival with allogeneic than with autologous HCT in AML patients with isolated trisomy 8: a study from the ALWP of the EBMT

Baron

Labopin

Blaise

et al. 2020

Bone Marrow Transplant

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The indication for performing an allogeneic hematopoietic stem cell transplantation (allo-HCT) in patients with isolated trisomy 8 AML in first complete remission (CR) is still debated. Here, we compared outcomes of such patients given either allo-HCT or autologous (auto)-HCT. Inclusion criteria consisted of adult patients with de novo AML, isolated trisomy 8, first HCT between 2000 and 2018, CR1 at transplantation, and either auto-HCT or allo-HCT with a HLA-identical sibling donor (MSD) or a 10/10 HLA-matched unrelated donor (UD 10/10). A total of 401 patients met the inclusion criteria. They underwent an auto-HCT (n = 81), allo-HCT with a MSD (n = 186) or allo-HCT with a 10/10 UD (n = 134). At 3 years, relapse incidence, nonrelapse mortality and leukemia-free survival (LFS) were 59%, 5%, and 37%, respectively, in auto-HCT recipients; 31% (P < 0.001), 14% (P = 0.04), and 55% (P = 0.033), respectively, in MSD recipients and 29% (P < 0.001), 13% (P = 0.15), and 59% (P = 0.03), respectively, in UD 10/10 recipients. In multivariate analysis, in comparison to auto-HCT, MSD and UD 10/10 were associated with a lower risk of relapse (HR = 0.47, P < 0.001 and HR = 0.40, P < 0.001, respectively) translating to better LFS (HR = 0.69, P = 0.04 and HR = 0.60, P = 0.03, respectively). There was also a similar trend for overall survival (HR = 0.73, P = 0.12 and HR = 0.65, P = 0.08).

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“…The patient was then transferred to the King Fahd Specialist Hospital, wherein molecular analysis, bone marrow analysis, karyotyping and immunophenotyping were performed. The cytogenetics report (Table II) of bone marrow aspirates indicated the presence of an abnormal tumoral clone with trisomy 8 (47, XX, +8 [18]/46, XX [1]); this karyotype was confirmed by fluorescence in situ hybridization, which showed 88% trisomy 8 (Data not shown); a karyotype abnormality that is associated with a moderate risk of AML according to ELN (12).…”

Section: Rna Sequencing-based Identification Of Potential Targets In mentioning

confidence: 90%

RNA sequencing‑based identification of potential targets in acute myeloid leukemia: A case report

et al. 2020

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Acute myeloid leukemia (AML) refers to heterogenous types of blood cancer which possess a complicated genomic landscape, and multiple novel mutational alterations are frequently being reported. Herein, a case report of a 37-year old AML patient is presented, who was diagnosed following laboratory investigation after admission. The patient had thrombocytopenia, and three consecutive blast counts of 40, 30 and 41%, respectively. A blood sample was collected for whole-genome RNA sequencing to understand the transcriptomic profile at the time of diagnosis and compared with a matched female control. Gene expression was quantified using the RSEM software package. Bioinformatics analysis revealed a significant number of differentially expressed genes in the patient, suggesting a marked change in the transcriptomic landscape in this patient. By mining the bioinformatics data and screening the highly expressed genes with ≥80% probability of gene expression, four novel genes were highlighted that may serve as potential future targets in AML patients; Rh associated glycoprotein, succinate receptor 1, transmembrane-4 L-six family member-1 and ADGRA3, although further validation of their value is required.

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Trisomy 8 in acute myeloid leukemia

Cited by 31 publications

References 119 publications

Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12)

Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12)

Better leukemia-free survival with allogeneic than with autologous HCT in AML patients with isolated trisomy 8: a study from the ALWP of the EBMT

RNA sequencing‑based identification of potential targets in acute myeloid leukemia: A case report

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