Straight to the Point—The Novel Strategies to Cure Pediatric AML

Lejman, Monika; Dziatkiewicz, Izabela; Jurek, Mateusz

doi:10.3390/ijms23041968

Cited by 11 publications

(5 citation statements)

References 150 publications

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“…AML is a heterogeneous disease characterized by the presence of different collaborating cytogenetic and molecular aberrations. Cytogenetic analysis had implicated several recurrent chromosomal structural abnormalities for pediatric AML pathogenesis, including 11q23 (KMT2A) rearrangements (frequency: 20%), t(8;21) (q22; q22) (frequency: 10%–12%), inv (16) (p13.1q22) or t(16;16) (p13.1;q22) (frequency: 10%), t(8;16) (p11;p13) (frequency:10%), t(15;17) (q24.1;q21.2) (frequency: 5%–10%), and t(6;9) (p22;q34) (frequency:1.2%–4%) ( 3 ). These acquired genetic abnormalities played an essential role in the pathogenesis of AML.…”

Section: Discussionmentioning

confidence: 99%

“…A number of genetic mutations have been identified in pediatric AML, which are related to biological, clinical, and prognostic implications. These genes included RUNX1 , NPM1 , CEBPA , FLT3 , MYST3 , EVI1 , KIT , IDH1 and IDH2 , DDX41 , ETV6 , GATA2 , TP53, and BCOR / BCORL1 ( 2 , 3 ). The BCL6 corepressor ( BCOR ) gene, and its homolog, the BCL6 corepressor-like 1 ( BCORL1 ) mutations, mostly represented frameshifts (deletions, insertions), nonsense and missense mutations, which led to the lack or low expression of the protein.…”

Section: Introductionmentioning

confidence: 99%

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BCORL1 S878G, GNB1 G116S, SH2B3 A536T, and KMT2D S3708R tetramutation co-contribute to a pediatric acute myeloid leukemia: Case report and literature review

Wang

Chen²,

Shen³

et al. 2022

Front. Pediatr.

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Acute myeloid leukemia (AML) is a clinically, morphologically, and genetically heterogeneous group of malignancies characterized by a wide range of genomic alterations responsible for defective regulation of the differentiation and self-renewal programs of hematopoietic stem cells. Here, we report a 4-month-old boy who had acute onset with leukocytosis and abdominal mass. The morphological analysis of bone marrow (BM) smear revealed extremely marrow hyperplasia, large quantities of immature cells, and primary and immature monocytic hyperplasia accounting for 57.5% of nucleated cells. The chromosome karyotype of the case was complex, representing 48, XY, +13, +19[12]/48, idem, del (p12)[8]. After RNAs sequencing, a mutation (c.346G > A, p.G116S) of the GNB1 gene was detected and localized to the mutational hotspot in Exon 7. Meanwhile, the other three mutations were identified by next-generation sequencing (NGS) and whole-exome sequencing (WES) of DNA from the BM aspirate and oral swab, including BCORL1 mutation [c.2632A > G, p.S878G, mutation allele frequency (VAF): 99.95%], SH2B3 mutation (c.1606G > A, p.A536T, VAF: 51.17%), and KMT2D mutation (c.11124C > G, p.S3708R, VAF: 48.95%). BCORL1 mutations have been associated with the pathogenesis of AML, whereas other mutations have rarely been previously reported in pediatric AML. The patient did not undergo the combination chemotherapy and eventually died of respiratory failure. In conclusion, the concurrence of BCORL1, GNB1, SH2B3, and KMT2D mutations may be a mutationally detrimental combination and contribute to disease progression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BCORL1 S878G, GNB1 G116S, SH2B3 A536T, and KMT2D S3708R tetramutation co-contribute to a pediatric acute myeloid leukemia: Case report and literature review

Wang

Chen²,

Shen³

et al. 2022

Front. Pediatr.

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“…Besides the classic genetic alterations, one can be surprised with unusual findings. 3,4 We describe a case of pediatric AML that generated deep discussion.…”

Section: E T T E R T O T H E E D I T O R Nup214::abl1: a Ph-like Fusi...mentioning

confidence: 99%

NUP214::ABL1: A Ph‐like fusion found in a pediatric acute myeloid leukemia patient with normal karyotype

Mota

Tesser-Gamba

Pires

et al. 2023

Pediatric Blood & Cancer

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The NUP214::ABL1 fusion is the second most common translocation involving the gene ABL1, after BCR::ABL1. It is a cryptic fusion in conventional karyotype, but detectable by molecular methods with specific probes. 8 It can be seen in B cell acute lymphoblastic leukemia (ALL) and less common in T cell ALL. 9,10 ABL1-a tyrosine kinase protein-is localized in 9q34.13 and NUP214-a component of the nuclear pore complex-in 9q34.12. There is a model that NUP214::ABL1 formation comes from a circularized region that segregated unequally during cellular division. 8 It is included in the Ph-like ALL group and may benefit from the use of tyrosine kinase inhibitors (TKI) such as dasatinib. [11][12][13] It is not seen among AML patients. There is just one previous case of NUP214::ABL1 in a 42-year-old patient in China. 14 This is the second description of the NUP214::ABL1 rearrangement found in AML, the first in the pediatric population. The lack of molecular methods availability impairs AML stratifying and this case was only better elucidated with the NGS on relapse. Even if other methods like protein chain reaction or fluorescence in situ hybridization were available, in this case, it hardly would be more enlightening, as this fusion is not routinely screened in AML. Moreover, his final classification is still defined by differentiation, as it is not otherwise specified. Perhaps there will be more cases described in the future, as the molecular tools become more accessible. Collecting cases like this one is extremely important for better understanding and discussing target therapies in future. The benefit of the use of TKI in this case remains an unanswered question. The more the stratifying tools are available worldwide, the better we will be able to personalize treatment. ACKNOWLEDGMENTSThe family gave written informed consent for archiving material in a biobank, for molecular profiling and clinical studies. It has the approval by the Ethics Committee of Federal University of São Paulo.

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“… 7 The high mortality associated with pediatric AML is partly due to the heterogeneity of the disease and lack of specific tumor cell antigens, which makes modern targeted therapy less effective. 8 …”

Section: Introductionmentioning

confidence: 99%

Consolidative Proton Radiotherapy for Pediatric Extramedullary Ocular Acute Myeloid Leukemia

Bush,

Eslin,

Joyce

et al. 2024

International Journal of Particle Therapy

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Straight to the Point—The Novel Strategies to Cure Pediatric AML

Cited by 11 publications

References 150 publications

BCORL1 S878G, GNB1 G116S, SH2B3 A536T, and KMT2D S3708R tetramutation co-contribute to a pediatric acute myeloid leukemia: Case report and literature review

BCORL1 S878G, GNB1 G116S, SH2B3 A536T, and KMT2D S3708R tetramutation co-contribute to a pediatric acute myeloid leukemia: Case report and literature review

NUP214::ABL1: A Ph‐like fusion found in a pediatric acute myeloid leukemia patient with normal karyotype

Consolidative Proton Radiotherapy for Pediatric Extramedullary Ocular Acute Myeloid Leukemia

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