A complex MLL rearrangement identified five years after initial MDS diagnosis results in out-of-frame fusions without progression to acute leukemia

Meyer, Claus; Kowarz, Eric; Yip, Sze‐Fai; Wan, T. S. K.; Chan, TK; Dingermann, Theo; Chan, Li-Chong; Marschalek, Rolf

doi:10.1016/j.cancergen.2011.10.001

Cited by 9 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, these 16 unusual MLL rearrangements—where neither any dimerization nor a transcriptional activation domain is present—probably represent a subclass of MLL abnormalities, which have per se no or only a weak ability to transform hematopoietic cells and are only identified in the context of other genetic abnormalities in hematopoietic stem cells. 33 , 34 …”

Section: Resultsmentioning

confidence: 99%

The MLL recombinome of acute leukemias in 2017

et al. 2017

View full text Add to dashboard Cite

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. 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.

show abstract

Section: Resultsmentioning

confidence: 99%

The MLL recombinome of acute leukemias in 2017

et al. 2017

View full text Add to dashboard Cite

show abstract

“…(Table 1 , #98, Table 2E ). Therefore, these 37 KMT2A rearrangements (Table 1 , #95–98) probably represent a subclass of KMT2A abnormalities for which other genetic abnormalities may account for the transformed phenotype of the leukemia cells [ 34 , 35 ].…”

Section: Resultsmentioning

confidence: 99%

The KMT2A recombinome of acute leukemias in 2023

et al. 2023

View full text Add to dashboard Cite

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5’-KMT2A, two patients had a 5’-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.

show abstract

“…Also the lysine methyltransferase 2A (KMT2A, formerly known as MLL) gene on 11q23.3 sometimes fuses with intergenic sequences of various chromosomes giving rise to out-of-frame KMT2A-fusion transcripts (146)(147)(148)(149). Based on the MLL recombinome data, five chromosome translocations exist that result in fusion of the 5′-part of KTM2A with genomic sequences from 1p13, 6q27, 9p13, 11q23, 11q24, and 21q22 (148,149) whereas ten chromosome translocations result in out-of-frame KMT2A fusion genes (146)(147)(148)(149).…”

Section: Abstract Chromosomal Translocations In Cancer As Well As Ben...mentioning

confidence: 99%