Genomic landscape of pediatric B-other acute lymphoblastic leukemia in a consecutive European cohort

Žaliová, Markéta; Stuchlý, Jan; Winkowska, Lucie; Musilová, Alena; Fišer, Karel; Slámová, Martina; Starková, Júlia; Vašková, Martina; Hrušák, Ondřej; Šrámková, Lucie; Starý, Jan; Zuna, Jan; Trka, Jan

doi:10.3324/haematol.2018.204974

Cited by 94 publications

(98 citation statements)

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“…ACIN1‐NUTM1 fusions have now also been reported on several more occasions in infant and pediatric ALLs . Other NUTM1 fusion partners reported in ALL are IKZF1 , ZNF618 , AFF1 , SLC12A6 , CUX1 , and BPTF …”

Section: Nutm1‐associated Allmentioning

confidence: 89%

Emerging entities in NUTM1‐rearranged neoplasms

McEvoy

Fox

Prall

2020

Genes Chromosomes & Cancer

106

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Structural alterations of NUTM1 were originally thought to be restricted to poorly differentiated carcinomas with variable squamous differentiation originating in the midline organs of children and adolescents. Termed NUT carcinomas (NCs), they were defined by a t(15;19) chromosomal rearrangement that was found to result in a BRD4‐NUTM1 gene fusion. However, the use of DNA and RNA‐based next‐generation sequencing has recently revealed a multitude of new NUTM1 fusion partners in a diverse array of neoplasms including sarcoma‐like tumors, poromas, and acute lymphoblastic leukemias (ALLs) that we propose to call NUTM1‐rearranged neoplasms (NRNs). Intriguingly, the nosology of NRNs often correlates with the functional classification of the fusion partner, suggesting different oncogenic mechanisms within each NRN division. Indeed, whereas NCs are characterized by their aggressiveness and intransigence to standard therapeutic measures, the more positive clinical outcomes seen in some sarcoma and ALL NRNs may reflect these mechanistic differences. Here we provide a broad overview of the molecular, nosological, and clinical features in these newly discovered neoplastic entities. We describe how aberrant expression of NUTM1 due to fusion with an N‐terminal DNA/chromatin‐binding protein can generate a potentially powerful chromatin modifier that can give rise to oncogenic transformation in numerous cellular contexts. We also conclude that classification, clinical behavior, and therapeutic options may be best defined by the NUTM1 fusion partner rather than by tumor morphology or immunohistochemical profile.

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Section: Nutm1‐associated Allmentioning

confidence: 89%

Emerging entities in NUTM1‐rearranged neoplasms

McEvoy

Fox

Prall

2020

Genes Chromosomes & Cancer

106

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“…The long tail distribution phenomenon of FGs has also been supported by several other systematic research reports. [12][13][14] Another feature of the long tail phenomenon is that the total positive rate of all singly relatively rare FGs is actually not low due to their wide variety and numerous members. 13,14 To date, the exact population of FGs undiscovered in hematological malignancies and the total positive rate of them remain unknown.…”

Section: Traditional Methods and Limitations Of Fgs Identificationmentioning

confidence: 99%

Advances in Fusion Gene Research and Fusion Gene Families in Hematological Malignancies

Chen

Wang

et al. 2019

Int J Med Rev

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Fusion genes (FGs) are major molecular biological abnormalities in hematological malignancies and have become well-established molecular markers for disease classification, risk stratification, and targeted therapies. The long tail phenomenon is observed in the distribution of FGs, which means that except for dozens of the most common FGs, the positive rates of the other FGs are all below 1%, even if they have been frequently reported in the literature. However, the total positive rate of these singly relatively rare FGs is actually not low due to their wide variety and numerous members. We therefore put forward the conception "fusion gene family, FG-FM" to describe fusions that share one common protagonist gene with different partner genes. Most of the FGs in hematological malignancies discovered to date can be classified into about 20 major families. Based on the characteristics of the currently reported FGs, it can be expected that although a great many FGs may be identified in the future, the total number of FG-FMs is rather limited. FGs in the same FG-FM often have similarities in pathogenicity, clinical features, and treatment outcomes. Classifying FGs according to FG-FMs will aid in understanding their pathogenicity and optimizing detection schemes.

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“…23,24 Other Molecular Alterations Approximately 4% of BCR-ABL1-like B-ALL cases have mutations of genes (KRAS, NRAS, NF1, PTPN11, CBL1, BRAF) that activate RAS signaling. 13,22,25 It should be noted that these RAS-activating mutations are also observed in other subtypes of B-ALL, for example hyperdiploid, hypodiploid, KMT2A-rearranged, and relapsed B-ALL. [26][27][28] Rare kinase alterations involving NTRK3, FLT3, BLNK, FGFR1, DGKH, and PTK2B have also been identified.…”

Section: Jak-stat Pathway Alterationsmentioning

confidence: 99%

“…Although some cases with high expression of CRLF2 by gene expression profiling are negative for CRLF2 rearrangement by FISH, studies have shown 100% correlation between expression of CRLF2 by flow cytometry and presence of CRLF2 rearrangement by FISH. 24,25,34 Cases testing negative for CRLF2 expression by classical cytogenetics and standard FISH panel can be further studied by a targeted FISH panel for genes involved in the kinase alterations (break-apart probes): ABL1, ABL2, PDGFRB, and JAK2. IKZF1 deletion study by FISH can also be included in this panel for prognostic information.…”

Section: Diagnosismentioning

confidence: 99%

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BCR-ABL1–like B-Acute Lymphoblastic Leukemia/Lymphoma: A Comprehensive Review

Jain

Abraham

2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.— In the 2016 update of the World Health Organization (WHO) classification of hematopoietic neoplasms, BCR-ABL1–like B-acute lymphoblastic leukemia/lymphoma (B-ALL) is added as a new provisional entity that lacks the BCR-ABL1 translocation but shows a pattern of gene expression very similar to that seen in B-ALL with BCR-ABL1. Objective.— To review the kinase-activating alterations and the diagnostic approach for BCR-ABL1–like B-ALL. Data Sources.— We provide a comprehensive review of BCR-ABL1–like B-ALL based on recent literature and the 2016 update of the World Health Organization classification of hematopoietic neoplasms. Conclusions.— Several types of kinase-activating alterations (fusions or mutations) are identified in BCR-ABL1–like B-ALL. The main categories are alterations in the ABL class family of genes, encompassing ABL1, ABL2, PDGFRB, PDGFRA (rare), and colony-stimulating factor 1 receptor ( CSF1R) fusions, or the JAK2 class family of genes, encompassing alterations in JAK2, CRLF2, EPOR, and other genes in this pathway. These alterations determine the sensitivity to tyrosine kinase inhibitors. As a wide variety of genomic alterations are included in this category, the diagnosis of BCR-ABL1–like B-ALL is extremely complex. Stepwise algorithms and comprehensive unbiased testing are the 2 ways to approach the diagnosis of BCR-ABL1–like B-ALL.

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Genomic landscape of pediatric B-other acute lymphoblastic leukemia in a consecutive European cohort

Cited by 94 publications

References 50 publications

Emerging entities in NUTM1‐rearranged neoplasms

Emerging entities in NUTM1‐rearranged neoplasms

Advances in Fusion Gene Research and Fusion Gene Families in Hematological Malignancies

BCR-ABL1–like B-Acute Lymphoblastic Leukemia/Lymphoma: A Comprehensive Review

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