<scp>MYB</scp> rearrangements and over‐expression in T‐cell acute lymphoblastic leukemia

Bardelli, Valentina; Arniani, Silvia; Pierini, Valentina; Pierini, Tiziana; Giacomo, Danika Di; Gorello, Paolo; Moretti, Martina; Pellanera, Fabrizia; Elia, Loredana; Vitale, Antonella; Storlazzi, Clelia Tiziana; Tolomeo, Doron; Mastrodicasa, Elena; Caniglia, Maurizio; Chiaretti, Sabina; Ruggeri, Loredana; Roti, Giovanni; Schwab, Claire; Harrison, Christine J.; Almeida, André Pedro Pinto De; Pieters, Tim; Vlierberghe, Pieter Van; Mecucci, Cristina; Starza, Roberta La

doi:10.1002/gcc.22943

Cited by 13 publications

(14 citation statements)

References 18 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, the dup(6)(q23.3q23.3) causes duplication of HBS1L and AHI1 gene segments, as well as the duplication and increased expression of MYB gene, whereas deregulation of MYB expression is involved in the pathogenesis of leukemia and lymphoma. [25][26][27][28] On the other hand, Abelson Helper Integration Site-1 (AHI1) is a novel oncogene. Aberrant expression of AHI1 is found in several human leukemic cell lines of myeloid, B-cell, and T-cell origin and contributes to leukemia and lymphoma development.…”

Section: Discussionmentioning

confidence: 99%

“…Although further analysis did not predict the formation of fusion proteins, there were some clues to lymphomagenesis. For instance, the dup(6)(q23.3q23.3) causes duplication of HBS1L and AHI1 gene segments, as well as the duplication and increased expression of MYB gene, whereas deregulation of MYB expression is involved in the pathogenesis of leukemia and lymphoma 25–28 . On the other hand, Abelson Helper Integration Site-1 ( AHI1 ) is a novel oncogene.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma

Xu,

Gao,

Wang

et al. 2023

Journal of Pediatric Hematology/Oncology

View full text Add to dashboard Cite

Background: Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM. Methods: OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L::AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR. Results: In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L::AHI1 and GRIK1::NSDHL, which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction. Conclusions: Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma

Xu,

Gao,

Wang

et al. 2023

Journal of Pediatric Hematology/Oncology

View full text Add to dashboard Cite

show abstract

“…MYB has been shown to be over-expressed in patients with T-cell acute lymphoblastic leukemia (T-ALL). Similarly, MYB rearrangements were also detected in T-ALL patients [ 58 ]. Distal regulatory elements have also been shown to regulate MYB in human myeloid leukemia cell lines [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs in Leukemias: A Clinically Annotated Compendium

Turk

Calin

Kunej

2022

IJMS

View full text Add to dashboard Cite

Leukemias are a group of malignancies of the blood and bone marrow. Multiple types of leukemia are known, however reliable treatments have not been developed for most leukemia types. Furthermore, even relatively reliable treatments can result in relapses. MicroRNAs (miRNAs) are a class of short, noncoding RNAs responsible for epigenetic regulation of gene expression and have been proposed as a source of potential novel therapeutic targets for leukemias. In order to identify central miRNAs for leukemia, we conducted data synthesis using two databases: miRTarBase and DISNOR. A total of 137 unique miRNAs associated with 16 types of leukemia were retrieved from miRTarBase and 86 protein-coding genes associated with leukemia were retrieved from the DISNOR database. Based on these data, we formed a visual network of 248 miRNA-target interactions (MTI) between leukemia-associated genes and miRNAs associated with ≥4 leukemia types. We then manually reviewed the literature describing these 248 MTIs for interactions identified in leukemia studies. This manually curated data was then used to visualize a network of 64 MTIs identified in leukemia patients, cell lines and animal models. We also formed a visual network of miRNA-leukemia associations. Finally, we compiled leukemia clinical trials from the ClinicalTrials database. miRNAs with the highest number of MTIs were miR-125b-5p, miR-155-5p, miR-181a-5p and miR-19a-3p, while target genes with the highest number of MTIs were TP53, BCL2, KIT, ATM, RUNX1 and ABL1. The analysis of 248 MTIs revealed a large, highly interconnected network. Additionally, a large MTI subnetwork was present in the network visualized from manually reviewed data. The interconnectedness of the MTI subnetwork suggests that certain miRNAs represent central disease molecules for multiple leukemia types. Additional studies on miRNAs, their target genes and associated biological pathways are required to elucidate the therapeutic potential of miRNAs in leukemia.

show abstract

“…Alterations typically observed in T-ALL, such as NOTCH1 or FBXW7 mutations, and CDKN2AB deletion, are present at a lower frequency than in adults and children, while new markers, such as the complete deletion of MLF1, appear to be specific and recurrent in iT-ALL [132]. Notably, the t(6;7)(q23;q34)/TRB-MYB, a very rare translocation in pediatric T-ALL (<3% of cases), was reported in three female patients with iT-ALL, displaying high white blood cell count, central nervous system involvement, and refractory disease or late relapse [134][135][136]. In addition, transcriptome and miRNome sequencing showed a clear separation between infant and pediatric T-ALL with 760 differentially expressed mRNAs and 58 differentially expressed miRNAs.…”

Section: Infant T-allmentioning

confidence: 99%

T-Cell Acute Lymphoblastic Leukemia: Biomarkers and Their Clinical Usefulness

Bardelli

Arniani

Pierini

et al. 2021

Genes

Self Cite

View full text Add to dashboard Cite

T-cell acute lymphoblastic leukemias (T-ALL) are immature lymphoid tumors localizing in the bone marrow, mediastinum, central nervous system, and lymphoid organs. They account for 10–15% of pediatric and about 25% of adult acute lymphoblastic leukemia (ALL) cases. It is a widely heterogeneous disease that is caused by the co-occurrence of multiple genetic abnormalities, which are acquired over time, and once accumulated, lead to full-blown leukemia. Recurrently affected genes deregulate pivotal cell processes, such as cycling (CDKN1B, RB1, TP53), signaling transduction (RAS pathway, IL7R/JAK/STAT, PI3K/AKT), epigenetics (PRC2 members, PHF6), and protein translation (RPL10, CNOT3). A remarkable role is played by NOTCH1 and CDKN2A, as they are altered in more than half of the cases. The activation of the NOTCH1 signaling affects thymocyte specification and development, while CDKN2A haploinsufficiency/inactivation, promotes cell cycle progression. Among recurrently involved oncogenes, a major role is exerted by T-cell-specific transcription factors, whose deregulated expression interferes with normal thymocyte development and causes a stage-specific differentiation arrest. Hence, TAL and/or LMO deregulation is typical of T-ALL with a mature phenotype (sCD3 positive) that of TLX1, NKX2-1, or TLX3, of cortical T-ALL (CD1a positive); HOXA and MEF2C are instead over-expressed in subsets of Early T-cell Precursor (ETP; immature phenotype) and early T-ALL. Among immature T-ALL, genomic alterations, that cause BCL11B transcriptional deregulation, identify a specific genetic subgroup. Although comprehensive cytogenetic and molecular studies have shed light on the genetic background of T-ALL, biomarkers are not currently adopted in the diagnostic workup of T-ALL, and only a limited number of studies have assessed their clinical implications. In this review, we will focus on recurrent T-ALL abnormalities that define specific leukemogenic pathways and on oncogenes/oncosuppressors that can serve as diagnostic biomarkers. Moreover, we will discuss how the complex genomic profile of T-ALL can be used to address and test innovative/targeted therapeutic options.

show abstract

MYB rearrangements and over‐expression in T‐cell acute lymphoblastic leukemia

Cited by 13 publications

References 18 publications

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma

MicroRNAs in Leukemias: A Clinically Annotated Compendium

T-Cell Acute Lymphoblastic Leukemia: Biomarkers and Their Clinical Usefulness

Contact Info

Product

Resources

About