The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis

Daser, Angelika; Rabbitts, Terence H.

doi:10.1016/j.semcancer.2005.01.007

Cited by 119 publications

(118 citation statements)

References 115 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…This is in line with recently published data on the frequency and distribution of different MLL fusion partner genes. 13,14 Breakpoint distribution according to clinical subtypes…”

Section: Identification Of Mll Rearrangements and Their Distribution mentioning

confidence: 99%

New insights to the MLL recombinome of acute leukemias

et al. 2009

View full text Add to dashboard Cite

Chromosomal rearrangements of the human MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemias. These patients need to be identified, treated appropriately and minimal residual disease was monitored by quantitative PCR techniques. Genomic DNA was isolated from individual acute leukemia patients to identify and characterize chromosomal rearrangements involving the human MLL gene. A total of 760 MLL-rearranged biopsy samples obtained from 384 pediatric and 376 adult leukemia patients were characterized at the molecular level. The distribution of MLL breakpoints for clinical subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, pediatric and adult) and fused translocation partner genes (TPGs) will be presented, including novel MLL fusion genes. Combined data of our study and recently published data revealed 104 different MLL rearrangements of which 64 TPGs are now characterized on the molecular level. Nine TPGs seem to be predominantly involved in genetic recombinations of MLL: AFF1/AF4, MLLT3/ AF9, MLLT1/ENL, MLLT10/AF10, MLLT4/AF6, ELL, EPS15/AF1P, MLLT6/AF17 and SEPT6, respectively. Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements.

show abstract

“…This is in line with recently published data on the frequency and distribution of different MLL fusion partner genes. 13,14 Breakpoint distribution according to clinical subtypes…”

Section: Identification Of Mll Rearrangements and Their Distribution mentioning

confidence: 99%

New insights to the MLL recombinome of acute leukemias

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Rearrangements involving MLL fusion genes, generated as a consequence of chromosomal translocations fusing N-terminal sequences of MLL to 1 of over 40 functionally diverse group of C-terminal fusion partners (Daser and Rabbitts, 2005), constitute 5% of all AML cases and 22% of those with acute lymphoblastic leukemia (De Braekeleer et al, 2005). Gene expression analyses revealed HOX gene dysregulation in all types of MLL fusion-associated T-and B-cell acute lymphoblastic leukemias (Rozovskaia et al, 2001;Armstrong et al, 2002;Yeoh et al, 2002;Ferrando et al, 2003), implicating HOX genes as integral factors in MLL fusion-associated leukemias.…”

Section: Mll Fusion Genesmentioning

confidence: 99%

Hox genes in hematopoiesis and leukemogenesis

2007

View full text Add to dashboard Cite

“…Modeling MLL-AF4 þ infant pro-B ALL using hESCs MLL-AF4 leukemogenesis has been particularly difficult to model 90 and bona fide MLL-AF4 disease models do not exist as of yet. Our little understanding of transformation by MLL fusions and their mode of action come from murine models.…”

Section: Environmental Exposures and Delayed Infection Early In Life mentioning

confidence: 99%

Insights into the cellular origin and etiology of the infant pro-B acute lymphoblastic leukemia with MLL-AF4 rearrangement

et al. 2010

View full text Add to dashboard Cite

Infant acute lymphoblastic leukemia (ALL) involving mixedlineage leukemia (MLL) fusions has attracted a huge interest in basic and clinical research because of its prenatal origin, mixed-lineage phenotype, dismal prognosis and extremely short latency. Over 90% of infant ALLs are pro-B ALL harboring the leukemic fusion MLL-AF4. Despite the fact that major achievements have provided a better understanding about the etiology of infant MLL-AF4 þ ALL over the last two decades, key questions remain unanswered. Epidemiological and genetic studies suggest that the in utero origin of MLL rearrangements in infant leukemia may be the result of prenatal exposure to genotoxic compounds. In fact, chronic exposure of human embryonic stem cells (hESCs) to etoposide induces MLL rearrangements and makes hESC more prone to acquire subsequent chromosomal abnormalities than postnatal CD34 þ cells, linking embryonic exposure to topoisomerase II inhibitors to genomic instability and MLL rearrangements. Unfortunately, very little is known about the nature of the target cell for transformation. Neuron-glial antigen 2 expression was initially claimed to be specifically associated with MLL rearrangements and was recently shown to be readily expressed in CD34 þ CD38 þ , but not CD34 þ CD38À cells suggesting that progenitors rather than stem cells may be the target cell for transformation. Importantly, the recent findings showing that MLL-AF4 rearrangement is present and expressed in mesenchymal stem cells from infant patients with MLLAF4 þ ALL challenged our current view of the etiology and cellular origin of this leukemia. It becomes therefore crucial to determine where the leukemia relapses come from and how the tumorstroma relationship is defined at the molecular level. Finally, MLL-AF4 leukemogenesis has been particularly difficult to model and bona fide MLL-AF4 disease models do not exist so far. It is likely that the current disease models are missing some essential ingredients of leukemogenesis in the human embryo/ fetus. We thus propose modeling MLL-AF4 þ infant pro-B ALL using prenatal hESCs.

show abstract

The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis

Cited by 119 publications

References 115 publications

New insights to the MLL recombinome of acute leukemias

New insights to the MLL recombinome of acute leukemias

Hox genes in hematopoiesis and leukemogenesis

Insights into the cellular origin and etiology of the infant pro-B acute lymphoblastic leukemia with MLL-AF4 rearrangement

Contact Info

Product

Resources

About