KMT2A (MLL) rearrangements observed in pediatric/young adult T‐lymphoblastic leukemia/lymphoma: A 10‐year review from a single cytogenetic laboratory

  title={KMT2A (MLL) rearrangements observed in pediatric/young adult T‐lymphoblastic leukemia/lymphoma: A 10‐year review from a single cytogenetic laboratory},
  author={Jess F Peterson and Linda B. Baughn and Kathryn E. Pearce and Cynthia M. Williamson and Jonna C Benevides Demasi and R. Michael Olson and Tony A Goble and Reid G. Meyer and Patricia T Greipp and Rhett P Ketterling},
  pages={541 - 546}
T‐lymphoblastic leukemia/lymphoma (T‐ALL/LBL) accounts for approximately 15% of pediatric and 25% of adult ALL. While the underlying frequency of KMT2A (MLL) gene rearrangements has been identified in approximately 4‐8% of T‐ALL/LBL cases, a paucity of literature is available to characterize further the KMT2A rearrangements in pediatric/young adult T‐ALL/LBL. A 10‐year retrospective review was performed to identify KMT2A rearrangements in specimens sent for T‐ALL/LBL fluorescence in situ… 
Acute leukemias harboring KMT2A/MLLT10 fusion: a 10‐year experience from a single genomics laboratory
The MLLT10 (formerly AF10) gene is the fourth most common KMT2A fusion partner across all acute leukemias and requires at least 3 breaks to form an in‐frame KMT2A/MLLT10 fusion due to the opposite
Rare KMT2A-ELL and Novel ZNF56-KMT2A Fusion Genes in Pediatric T-cell Acute Lymphoblastic Leukemia
K MT2A-ELL fusion is a rare recurrent genetic event in T-ALL with uncertain prognostic implications and the frequency and impact of ZNF56-KMT2A in T -ALL are unknown.
Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins
Fusion transcripts status in T-ALL can be robustly identified by RT-MLPA, facilitating risk adapted treatment strategies for high-risk patients.
A novel deletion mutation in KMT2A identified in a child with ID/DD and blood eosinophilia
This is the first report of a rare case with ID/DD as well as eosinophilia, resulting from a previously undescribed null mutation of KMT2A, and the findings expand the phenotypical spectrum in affected individuals with K MT2A mutations.
Comprehensive Overview of Gene Rearrangements in Childhood T-Cell Acute Lymphoblastic Leukaemia
This study focuses on new potential therapeutic targets and predictive factors which may improve the outcome of young patients with T-ALL, as molecular biology techniques provide insights into the biology of cancer.
MLLT10 rearranged acute leukemia: Incidence, prognosis, and possible therapeutic strategies
Understanding the underlying genomics of MLLT10r acute leukemia, both clinically and molecularly, will improve prognostic stratification and accelerate the development of targeted therapeutic strategies, to improve patient outcomes.
Human MLL/KMT2A gene exhibits a second breakpoint cluster region for recurrent MLL–USP2 fusions
Nearly, all breakpoints have been identified in the major breakpoint cluster region (BCR) of the MLL gene (MLL exons 8–14) and some of the patients remained negative, although they were positively prescreened by various methods.
RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia.
It is shown that RUNX2 acts as a dependency factor in high-risk subtypes of human T-ALL through concomitant regulation of tumour metabolism and leukemic cell migration.
Clinical and molecular consequences of fusion genes in myeloid malignancies
The history, biologic effect, and clinical impact of fusion genes in the field of myeloid leukemias are discussed and next‐generation sequencing has allowed additional insights into the nature of leukemic fusion genes.


Distinctive genotypes in infants with T‐cell acute lymphoblastic leukaemia
The data indicates that iT‐ALL has a diverse but distinctive profile of genotypic abnormalities when compared to T‐ALL in older children and adults.
MLL-Rearranged Leukemias—An Update on Science and Clinical Approaches
The normal biological roles of MLL1 and its fusion partners are discussed, how these roles are hypothesized to be dysregulated in the context of M LL1 rearrangements, and the clinical manifestations of this group of leukemias are discussed.
The MLL recombinome of acute leukemias in 2017
This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.
Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19)(q23;p13.3) translocation.
  • J. Rubnitz, B. Camitta, C. Pui
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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The results suggest that patients with this genetic abnormality who have T-cell ALL or are 1 to 9 years of age should not be considered candidates for hematopoietic stem-cell transplantation during their first remission.
Using integrated genomic analysis of 264 T-ALL cases, 106 putative driver genes are identified and new mechanisms of coding and noncoding alteration are described, which suggests that different signaling pathways have distinct roles according to maturational stage.
The MLL recombinome of acute leukemias
The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) was determined and several new TPGs were identified and two new MLL rearrangements are now characterized at the molecular level.
T-lymphoblastic leukemia/lymphoma.
It is important to recognize ETP-ALL, because these patients have a poor prognosis if treated with standard therapy and a consensus immunophenotype has been developed to aid in the recognition of these cases.
Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast
It is shown that the paradigm of multistep leukemogenesis is very much applicable to T-ALL and that the different genetic insults collaborate to maintain self-renewal capacity, and induce proliferation and differentiation arrest of T-lymphoblasts.
Development of five dual-color, double-fusion fluorescence in situ hybridization assays for the detection of common MLL translocation partners.
Dual-color, double-fusion fluorescence in situ hybridization (D-FISH) probe sets are designed to identify complex/unbalanced MLL/partner translocations occurring in pediatric patients versus adult patients and a normal cutoff of 0.6% was established, suggesting an application for these assays in minimal residual disease detection and disease monitoring.
Mouse models of MLL leukemia: recapitulating the human disease.
This review provides an overview of different MLL-FP mouse model systems and discusses how well they have recapitulated aspects of the human disease as well as highlights the biological insights each model has provided into M LL-FP leukemogenesis.