Infant T‐cell acute lymphoblastic leukaemia with t(6;7) (<i>TCRB‐MYB</i>) translocation

Ramdeny, Pemantah Sandheeah; Mullanfroze, Khushnuma; Lorenzo, Paola De; Valsecchi, Maria Grazia; Meijerink, Jules P.P.; Pieters, Rob; Baruchel, André; Vora, Ajay

doi:10.1111/bjh.17609

Cited by 4 publications

(1 citation statement)

References 5 publications

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“…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

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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.

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Section: Infant T-allmentioning

confidence: 99%

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

Bardelli

Arniani

Pierini

et al. 2021

Genes

View full text Add to dashboard Cite

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Cytogenetics in the management of T-cell acute lymphoblastic leukemia (T-ALL): Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH)

De Bie,

Quessada,

Tueur

et al. 2023

Current Research in Translational Medicine

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How I treat infant acute lymphoblastic leukemia

Bartram,

Ancliff,

Vora

2025

Blood

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Infant acute lymphoblastic leukemia (ALL) is an aggressive malignancy that has historically been associated with a very poor prognosis. Despite large co-operative international trials and incremental increases in intensity of therapy, there has been no significant improvement in outcome over the last 3 decades. Using representative cases, we highlight the key differences between KMT2A-rearranged and KMT2A-germline infant ALL, and how advances in molecular diagnostics are unpicking KMT2A-germline genetics and guiding treatment reduction. We focus on KM2TA-rearranged infant B-cell ALL where the last few years have seen the emergence of novel therapies which both are more effective and less toxic than conventional chemotherapy. Of these, there is promising early data on the efficacy and tolerability of the bi-specific T-cell engager monoclonal antibody, blinatumomab, as well as the use of autologous and allogeneic chimeric antigen receptor T-cell therapy. We discuss how we can improve risk stratification and incorporate these new agents to replace the most toxic elements of currently deployed intensive chemotherapy schedules with their associated unacceptable toxicity.

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Infant T‐cell acute lymphoblastic leukaemia with t(6;7) (TCRB‐MYB) translocation

Cited by 4 publications

References 5 publications

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

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

Cytogenetics in the management of T-cell acute lymphoblastic leukemia (T-ALL): Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH)

How I treat infant acute lymphoblastic leukemia

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