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

@article{Peterson2018KMT2AR,
  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},
  journal={Genes},
  year={2018},
  volume={57},
  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… 
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References

SHOWING 1-10 OF 23 REFERENCES
Distinctive genotypes in infants with T‐cell acute lymphoblastic leukaemia
TLDR
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
TLDR
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
TLDR
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
  • 1999
TLDR
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.
THE GENOMIC LANDSCAPE OF PEDIATRIC AND YOUNG ADULT T-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA
TLDR
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
TLDR
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.
TLDR
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
TLDR
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.
TLDR
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.
TLDR
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.
...
...