MLL Gene Alterations in Acute Myeloid Leukaemia (11q23/MLL+ AML)

Ilenčíková, Denisa; Kolenová, Alexandra

doi:10.5772/55141

Cited by 3 publications

(10 citation statements)

References 60 publications

(67 reference statements)

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“…The current cure rate for paediatric AMLs is approximately 65%, with a 5-year event-free survival probability ranging from 32-54% for MLL-rearranged AML patients [15]. MLL-rearranged AMLs are heterogeneous in nature, so the prognostic outcome is dependent on the translocation partner, white cell count, additional cytogenetic aberrations and early response to treatment [24].…”

Section: Discussionmentioning

confidence: 99%

“…The 19p13.1 and 19p13.3 breakpoints are not always cytogenetically distinguishable [4]; however, the 19p13.2 band was observed on the der(11) in this case (Figure 1), meaning the proband is likely to have the t(11;19)(q23;p13.1) rearrangement (11q+, 19p-) which results in an MLL/ELL gene fusion [7]. As the banding resolution was only 350bph, confirmation of the rearrangement by FISH [4] or PCR-based testing would be desirable, as the literature suggests the MLL/ELL (MEN) fusion protein does not have a direct leukemogenic effect whereas the MLL/ENL (MLLT1) protein does [3,15]. The proband is described as an AML with recurrent genetic abnormalities under the World Health Organisation (WHO) classification [16] due to the presence of an 11q23 MLL gene rearrangement (Figure 2).…”

Section: Methodsmentioning

confidence: 99%

“…The proband is described as an AML with recurrent genetic abnormalities under the World Health Organisation (WHO) classification [16] due to the presence of an 11q23 MLL gene rearrangement (Figure 2). Such AMLs are characteristically heterogeneous [15], with the MLL gene rearrangement thought to drive the disease, as the der(11) fusion transcript is always expressed, but the der(19) transcript may not be formed [17], as breaks in the breakpoint cluster of the MLL gene are often accompanied by downstream deletions [3]. It is currently assumed that the der (19) does not contribute to leukemagenesis for this reason [3,15], and also because the t (11;19) fusion gene and the chimeric protein that is formed is thought to be insufficient to cause leukemogenesis on its own [3,16].…”

Section: Methodsmentioning

confidence: 99%

“…ALLs are reported to have a higher white cell count (median 102 vs 25.9×10 9 /L) and shorter survival than AML patients due to an increased incidence of relapse [20], and MLL gene rearrangements occur in 66% of ALLs but only 35% of AMLs [20]. MLL gene rearrangements are thought to arise by multiple mechanisms, such as recombination mediated by VDJ, Alu elements, and DNA topoisomerase II, or by non-homologous end joining [3], and breaks in the MLL gene generally occur closer to the centromeric end of the MLL gene breakpoint cluster region (bcr) in de novo AMLs, compared to the telomeric end observed in infant leukaemia and t-AML [15]. It is unknown, however, if MLL gene breakpoint variation can contribute to differences in clinical presentation between ALL and AML patients with the t(11;19), as the incidence of the t (11;19) in ALL is 18% compared to 15% in AML [20] Several scenarios therefore seem plausible to explain the clinical presentation of the proband.…”

Section: Methodsmentioning

confidence: 99%

“…Aside from variation in the MLL breakpoint, other possibilities include the co-involvement of the 19p13 ELL gene in disease development, the presence of a treatment-related mutation in addition to the t (11;19), or the presence of an underlying mutation causing an overlapping AML/MDS syndrome. The fact that the alternate 19p13.3 MLL/ENL (MLLT1) fusion protein is known to have a direct leukemogenic effect [3,15], suggests that the 19p13 breakpoint does in fact play a role in disease development, so the contribution of the ELL gene to the clinical presentation of the disease must therefore be considered. ELL is an RNA polymerase II elongation factor and promotes transcription, and overexpression of ELL is reported to be toxic, so the gene may in fact be critical for cell growth regulation and survival [21].…”

Section: Methodsmentioning

confidence: 99%

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A paediatric patient with AML M1 and a t(11;19)(q23;p13.1) rearrangement

Duffy¹,

Gong²,

Cole³

et al. 2015

Integr Mol Med

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The t(11;19)(q23;p13) translocation is found in a variety of haematological malignancies, but most are present as either acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) with an M4 or M5 subtype. The t(11;19)(q23;p13.1) translocation results in a MLL/ELL(MEN) chimeric fusion gene and has only been reported in AMLs to date, with the majority occurring in adults. Few paediatric t(11;19)(q23;p13.1) cases have been reported. We present the case of a ten year old patient with AML, WHO subtype AML without maturation (FAB classification M1), who was found to have a t(11;19)(q23;p13.1) translocation on conventional cytogenetics, and an 11q23 MLL gene rearrangement on FISH. Although molecular studies to confirm the MLL/ELL gene fusion were not performed, the paucity of information about paediatric cases, and the uncertain contribution of MLL/ELL to leukemogenesis, makes this case of clinical interest. Results and discussionCytogenetic G-banding showed a 46,XX,t(11;19)(q23;p13.1) karyotype in 25 cells at the patient's initial presentation (Figure 1); the translocation was detected in 19/20 metaphase cells at her second presentation.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

A paediatric patient with AML M1 and a t(11;19)(q23;p13.1) rearrangement

Duffy¹,

Gong²,

Cole³

et al. 2015

Integr Mol Med

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Untitled

2017

BPOJ

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MLL is one of the most aggressive leukemias which mostly targets pediatric patients. Genetic rearrangement of the 11q23 location is the main reason for this type of acute leukemia. MLL gene and its fusion proteins have produced a core complex which leads to abnormal hematopoesis. Although many clinical and lab studies have been done to show the prominent role of MLL in leukemogenesis since its discovery in 1992, large-scale genomic data seems to be the most effective way to analyse the hematologic malignancies extensively. Gene expression, methylation, mutation, RNA-seq, and SNP arrays have updated the understanding of the transformation oncohematologic disorder mechanism. As a result of the genomic data analysis, new biomarkers may have been detected as therapy target genes and used for personalized medicine. The genomics-bioinformatics studies and novel technical advances provide some precious knowledge to discover novel therapeutic strategies and better treatment outcomes in the future.

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11q23/MLL rearrangements in adult acute leukemia

et al. 2023

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Summary. Aim: To detect the frequency, diagnostic and prognostic significance of 11q23/MLL rearrangements and to determine the chromosomes that are most frequently involved in 11q23/MLL abnormalities in adult acute leukemia (AL). Materials and Methods: Cytogenetic investigations of bone marrow and/or peripheral blood cells from 140 patients with acute myeloid leukemia (AML) and 57 patients with acute lymphoblastic leukemia (ALL) were performed. The methods of conventional cytogenetics (GTG-banding) and fluorescence in situ hybridization were used. Results: Chromosomal abnormalities in leukemia cells were found by conventional cytogenetic methods in 80 (57%) and 37 (65%) adult patients with AML and ALL, respectively. 11q23/MLL rearrangements were found in 7 (5%) and 8 (14%) patients with AML and ALL, respectively. Among them, 8 (53.4%) patients had translocations, 2 (13.3%) — had deletions and 5 (33.3%) patients had trisomies or tetrasomies of chromosome 11. With respect to the distribution of partner chromosomes involved in 11q23/MLL translocations chromosome 4 was found to participate in 3 (37.5%) cases of 11q23/MLL translocations, 9 — in 2 (25%) cases and chromosomes 10, 14 and non-identified chromosome were involved in 1 (12.5%) case each. Nine patients (60%), besides abnormal ones, had 9–86% normal metaphases in their karyotypes. Of 15 patients with 11q23/MLL rearrangements, 5 (33%) patients had only 11q23/MLL rearrangements, whereas other 10 (67%) — had additional cytogenetic abnormalities, besides 11q23/MLL rearrangements. Conclusions: Chromosomal abnormalities of various kinds were found in 57% and 65% adult patients with AML and ALL, respectively. The frequency of 11q23/MLL rearrangements in patients with AML and ALL was 5% and 14%, respectively. Since AL patients with 11q23/MLL rearrangements are attributed to cytogenetic categories of AL with a poor or intermediate risk prognosis, cytogenetic methods should be included in the standard examination of AL patients for diagnosis, prognosis and selection of the optimal treatment strategy.

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MLL Gene Alterations in Acute Myeloid Leukaemia (11q23/MLL+ AML)

Cited by 3 publications

References 60 publications

A paediatric patient with AML M1 and a t(11;19)(q23;p13.1) rearrangement

A paediatric patient with AML M1 and a t(11;19)(q23;p13.1) rearrangement

Untitled

11q23/MLL rearrangements in adult acute leukemia

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