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- Noort, S., et al.
(författare)
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Analysis of rare driving events in pediatric acute myeloid leukemia
- 2023
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 108:1, s. 48-60
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Tidskriftsartikel (refereegranskat)abstract
- Elucidating genetic aberrations in pediatric acute myeloid leukemia (AML) provides insight in biology and may impact on risk-group stratification and clinical outcome. This study aimed to detect such aberrations in a selected series of samples without known (cyto)genetic aberration using molecular profiling. A cohort of 161 patients was selected from various study groups: DCOG, BFM, SJCRH, NOPHO and AEIOP. Samples were analyzed using RNA sequencing (n=152), whole exome (n=135) and/or whole genome sequencing (n=100). In 70 of 156 patients (45%), of whom RNA sequencing or whole genome sequencing was available, rearrangements were detected, 22 of which were novel; five involving ERG rearrangements and four NPM1 rearrangements. ERG rearrangements showed self-renewal capacity in vitro, and a distinct gene expression pattern. Gene set enrichment analysis of this cluster showed upregulation of gene sets derived from Ewing sarcoma, which was confirmed comparing gene expression profiles of AML and Ewing sarcoma. Furthermore, NPM1-rearranged cases showed cytoplasmic NPM1 localization and revealed HOXA/B gene overexpression, as described for NPM1 mutated cases. Single-gene mutations as identified in adult AML were rare. Patients had a median of 24 coding mutations (range, 7-159). Novel recurrent mutations were detected in UBTF (n=10), a regulator of RNA transcription. In 75% of patients an aberration with a prognostic impact could be detected. Therefore, we suggest these techniques need to become standard of care in diagnostics.
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- Noort, Sanne, et al.
(författare)
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Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM Study Group.
- 2018
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 132:15, s. 1584-1592
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Tidskriftsartikel (refereegranskat)abstract
- To study the prognostic relevance of rare genetic aberrations in acute myeloid leukemia (AML), such as t(16;21), international collaboration is required. Two different types of t(16;21) translocations can be distinguished: t(16;21)(p11;q22), resulting in the FUS-ERG fusion gene; and t(16;21)(q24;q22), resulting in RUNX1-core binding factor (CBFA2T3). We collected data on clinical and biological characteristics of 54 pediatric AML cases with t(16;21) rearrangements from 14 international collaborative study groups participating in the international Berlin-Frankfurt-Münster (I-BFM) AML study group. The AML-BFM cohort diagnosed between 1997 and 2013 was used as a reference cohort. RUNX1-CBFA2T3 (n = 23) had significantly lower median white blood cell count (12.5 × 109/L, P = .03) compared with the reference cohort. FUS-ERG rearranged AML (n = 31) had no predominant French-American-British (FAB) type, whereas 76% of RUNX1-CBFA2T3 had an M1/M2 FAB type (M1, M2), significantly different from the reference cohort (P = .004). Four-year event-free survival (EFS) of patients with FUS-ERG was 7% (standard error [SE] = 5%), significantly lower compared with the reference cohort (51%, SE = 1%, P < .001). Four-year EFS of RUNX1-CBFA2T3 was 77% (SE = 8%, P = .06), significantly higher compared with the reference cohort. Cumulative incidence of relapse was 74% (SE = 8%) in FUS-ERG, 0% (SE = 0%) in RUNX1-CBFA2T3, compared with 32% (SE = 1%) in the reference cohort (P < .001). Multivariate analysis identified both FUS-ERG and RUNX1-CBFA2T3 as independent risk factors with hazard ratios of 1.9 (P < .0001) and 0.3 (P = .025), respectively. These results describe 2 clinically relevant distinct subtypes of pediatric AML. Similarly to other core-binding factor AMLs, patients with RUNX1-CBFA2T3 rearranged AML may benefit from stratification in the standard risk treatment, whereas patients with FUS-ERG rearranged AML should be considered high-risk.
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- Benetton, M., et al.
(författare)
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Molecular Measurable Residual Disease Assessment before Hematopoietic Stem Cell Transplantation in Pediatric Acute Myeloid Leukemia Patients: A Retrospective Study by the I-BFM Study Group
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell transplantation (HSCT) is a curative post-remission treatment in patients with acute myeloid leukemia (AML), but relapse after transplant is still a challenging event. In recent year, several studies have investigated the molecular minimal residual disease (qPCR-MRD) as a predictor of relapse, but the lack of standardized protocols, cut-offs, and timepoints, especially in the pediatric setting, has prevented its use in several settings, including before HSCT. Here, we propose the first collaborative retrospective I-BFM-AML study assessing qPCR-MRD values in pretransplant bone marrow samples of 112 patients with a diagnosis of AML harboring t(8;21)(q22; q22)RUNX1::RUNX1T1, or inv(16)(p13q22)CBFB::MYH11, or t(9;11)(p21;q23)KMT2A::MLLT3, or FLT3-ITD genetic markers. We calculated an ROC cut-off of 2.1 x 10(-4) that revealed significantly increased OS (83.7% versus 57.1%) and EFS (80.2% versus 52.9%) for those patients with lower qPCR-MRD values. Then, we partitioned patients into three qPCR-MRD groups by combining two different thresholds, 2.1 x 10(-4) and one lower cut-off of 1 x 10(-2), and stratified patients into low-, intermediate-, and high-risk groups. We found that the 5-year OS (83.7%, 68.6%, and 39.2%, respectively) and relapse-free survival (89.2%, 73.9%, and 67.9%, respectively) were significantly different independent of the genetic lesion, conditioning regimen, donor, and stem cell source. These data support the PCR-based approach playing a clinical relevance in AML transplant management.
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- Zhu, X, et al.
(författare)
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Changing Disparity of Gastric Cancer Incidence by Histological Types in US Race-Specific Populations
- 2020
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Ingår i: Cancer control : journal of the Moffitt Cancer Center. - : SAGE Publications. - 1526-2359. ; 27:1, s. 1073274820977152-
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Tidskriftsartikel (refereegranskat)abstract
- The incidence pattern of gastric cancer by histological types across major race/ethnic groups is unknown. Methods: Age-standardized rates from 1992-2016 by race/ethnicity were calculated using data from Surveillance, Epidemiology, and End Results Program (SEER). Annual percent changes (APCs) in rates and corresponding 95% confidence intervals (CIs) were calculated and pairwise comparison of rates between race/ethnic groups was performed using the Joinpoint Regression Program. Calendar periods of incidence rates of gastric cardia and non-cardia cancer by histological types across race/ethnicity groups were shown by figures. Results: The White population has the highest incidence of gastric cardia adenocarcinoma and the incidence is keeping constant from 1992 through 2016 except the decreasing in the Asian population (AAPC = −1.4, 95%CI (−2.1, −0.8)). Although the incidence of non-cardia adenocarcinoma is decreasing in each group, the descending trend in the Asian population is the quickest (AAPC = −3.8, 95%CI (−4.0, −3.5)). Gastric carcinoids were observed to have statistically significant increasing trends in all race/ethnicity groups, especially in Hispanic women from 0.4 per 100,000 to 1.6 per 100,000 persons. The incidence of gastrointestinal stromal tumors (GISTs) is rising, with Non-Hispanic blacks having the highest incidence. Conclusion: This study demonstrated disparities in the incidence of gastric cancer by histological types among different race/ethnic groups. Further investigations are warranted to understand the changing incidence patterns by race/ethnicity.
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