Coexistence of iAMP21 and ETV6-RUNX1 fusion in an adolescent with B cell acute lymphoblastic leukemia: literature review of six additional cases

Gu, Jun; Reynolds, Alexandra; Fang, Lianghua; DeGraffenreid, Corrie; Sterns, Kenneth; Patel, Keyur P.; Medeiros, L. Jeffrey; Lin, Pei; Lu, Xinyan

doi:10.1186/s13039-016-0294-0

Cited by 11 publications

(7 citation statements)

References 31 publications

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“…This abnormality has been confirmed to be a primary genetic event in B-ALL [ 16 ] and has been identified when three or more additional copies of RUNX1 ( AML1 ) are observed on a single abnormal chromosome 21 (including a total of five or more RUNX1 copies per cell) [ 10 , 17 ]. iAMP is a distinct marker caused by the breakage-fusion-bridge cycle and chromothripsis, which involves tens to hundreds of genomic rearrangements with multiple regions of gain, amplification, inversion, and deletion [ 10 , 18 , 19 ].…”

Section: Genomic Heterogeneity In Molecular Subtypes Of Allmentioning

confidence: 99%

New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Montaño

Forero-Castro

Marchena-Mendoza

et al. 2018

Cancers

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The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures. We reviewed the molecular basis of pathways including transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. The implementation of NGS strategies has enabled important mutated genes in each pathway, their associations with the genetic subtypes of ALL, and their outcomes, which will be described further. We also discuss classic and new cryptic DNA rearrangements in ALL identified by mRNA-seq strategies. Novel cooperative abnormalities in ALL could be key prognostic and/or predictive biomarkers for selecting the best frontline treatment and for developing therapies after the first relapse or refractory disease.

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Section: Genomic Heterogeneity In Molecular Subtypes Of Allmentioning

confidence: 99%

New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

Montaño

Forero-Castro

Marchena-Mendoza

et al. 2018

Cancers

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“…Recent update of WHO classification for hematologic malignancies defined additional new category of BCP-ALL with aberrations of chromosome 21 that is intrachromosomal amplification of chromosome 21 (iAMP21) (Wenzinger et al 2018). In contrary to aforementioned changes concerning chromosome 21, iAMP21 is known to be negative predictive and prognostic factor (Heerema et al 2013; Harrison et al 2014; Gu et al 2016; Kim et al 2016; Yang et al 2017) if not treated with high-risk protocol.…”

Section: Introductionmentioning

confidence: 95%

“…Genetic abnormalities of the chromosome 21 are the most common findings among children diagnosed with B cell precursor acute lymphoblastic leukemia (BCP-ALL) (Li et al 2014a; Johnson et al 2015). Molecular subtypes of BCP-ALL with changes in the chromosome 21 are in majority connected with good prognosis, e.g., hyperdiploidy with chromosome 21 multiplication or ETV6-RUNX1 fusion t(12;21)(p13.2;q22.q) (Depil et al 1998; Harewood et al 2003) with 5-year survival rates exceeding 90% in both cases (Brown et al 2007; Vora et al 2013, 2014; Gu et al 2016; Moorman 2016). Recent update of WHO classification for hematologic malignancies defined additional new category of BCP-ALL with aberrations of chromosome 21 that is intrachromosomal amplification of chromosome 21 (iAMP21) (Wenzinger et al 2018).…”

Section: Introductionmentioning

confidence: 99%

MLPA as a complementary tool for diagnosis of chromosome 21 aberrations in childhood BCP-ALL

et al. 2019

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Chromosome 21 abnormalities are the most frequent genetic findings in childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL) cases. Majority of patients are effectively diagnosed with fluorescence in situ hybridization (FISH) and karyotyping; however, some cases may require additional tools to be used. Bone marrow samples of 373 childhood BCP-ALL patients were tested for chromosome 21 copy number variations (CNVs) with Multiplex Ligation-dependent Probe Amplification (MLPA) P327 array. Results from MLPA and cytogenetics were compared between groups according to the type of abnormality found on chromosome 21. Out the group of 235 patients, chromosome 21 multiplication was found by FISH assay in 56 cases (23.81%), ETV6-RUNX1 fusion in 34 (14.47%) and iAMP21 in 3 (1.28%) children, remaining 142 (60.43%) patients had no known chromosome 21 aberration. Median peak ratios of all tested probes in MLPA in aforementioned groups were 1.47 (IQR 1.28–1.77) vs. 1.00 (IQR 1.00–1.09) vs. 2.79 (IQR 1.97–2.83) vs. 1.00 (1.00–1.11), respectively. Aforementioned peak ratio of ETV6-RUNX1 fusion group was similar with patients of no known chromosome 21 aberration (p = 0.71). Interestingly, both groups differed from patients with chromosome 21 multiplication (p < 10−5) and with iAMP21 (p < 10−5). All cases of iAMP21 were correctly recognized by MLPA. MLPA seems to be good additional tool in the diagnostic process of chromosome 21 CNVs, especially in cases with iAMP21.

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“…[ 5 6 ] These genetic abnormalities play a critical role in the prognosis and treatment of the disease. [ 6 7 ]…”

Section: Introductionmentioning

confidence: 99%

Molecular detection of fusion oncogenes in zambian patients with acute lymphoblastic leukemia

Okuku

Kwenda

Samutela

et al. 2020

Int J App Basic Med Res

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Introduction: Chromosomal aberrations play a significant role in the pathogenesis of acute lymphoblastic leukemia (ALL) with prognostic and therapeutic implications. Despite the availability of molecular tools, low-resource settings struggle to diagnose the disease due to limited diagnostic capacity. The objective of this study was to detect common chromosomal aberrations in patients with ALL attending the University Teaching Hospital (UTH) in Lusaka, Zambia. Materials and Methods: In this prospective study, 19 blood samples from patients with ALL were screened for the presence of BCR-ABL, E2A-PBX1, MLL-AF4, and ETV6-RUNX1 fusion oncogenes using reverse transcriptase-polymerase chain reaction assay. Blood counts and clinical characteristics of patients were also assessed. Results: The age of patients ranged from 1½ to 72 years and comprised 57.9% of males and 42.1% of females. The majority of these patients were children (68%), and adults only comprised 32%. Only BCR-ABL and E2A-PBX1 oncogenes were detected in 3/19 of cases. The BCR-ABL gene was detected in a 4-year-old female child and a 15-year-old child. Both cases were associated with hepatomegaly and anemia coupled with low hemoglobin, white blood cell, and platelet counts. E2A-PBX1 was detected in a 12-year-old child with lymphadenopathy and splenomegaly, coupled with low hemoglobin, white blood cell, and platelet counts. All the three patients who harbored these fusion oncogenes died. Conclusion: This is the first study from Zambia to investigate the presence of fusion oncogenes in leukemia patients, which were found only among the older children population. Based on these findings, we recommend that molecular diagnosis be made a priority for the younger leukemia patient population at UTH.

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Coexistence of iAMP21 and ETV6-RUNX1 fusion in an adolescent with B cell acute lymphoblastic leukemia: literature review of six additional cases

Cited by 11 publications

References 31 publications

New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update

MLPA as a complementary tool for diagnosis of chromosome 21 aberrations in childhood BCP-ALL

Molecular detection of fusion oncogenes in zambian patients with acute lymphoblastic leukemia

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