Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML

@article{Schnittger2000ScreeningFM,
  title={Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML},
  author={S. Schnittger and U. Kinkelin and C. Schoch and A. Heinecke and D. Haase and T. Haferlach and T. Büchner and B. W{\"o}rmann and W. Hiddemann and F. Griesinger},
  journal={Leukemia},
  year={2000},
  volume={14},
  pages={796-804}
}
Partial tandem duplications of the MLL gene have been associated with trisomy 11 in acute myeloid leukemia (AML) and recently, have also been reported for karyotypically normal AML. In order to test the incidence and prognostic importance of this molecular marker, we have analyzed eight cases of AML with trisomy 11 and 387 unselected consecutive cases with AML for partial duplications of the MLL gene. Patients with normal karyotypes and those with various chromosome aberrations were included… Expand
Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia
TLDR
Although there is an overlap in the mutational spectrum in AML with FLT3 ITD and MLL PTD mutations, the data do not support a common mechanistic basis and do not unequivocally support the notion that MLLPTD mutations represent an independent prognostic factor. Expand
Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23
TLDR
Partial tandem duplication of the MLL gene is associated with increased expression of CD11b on leukemic blasts and implicates poor prognosis in adult AML patients and the higher frequency of MLL duplication in children older than 1 year, than in other age groups, needs to be confirmed by further studies. Expand
Identification of Partial Tandem Duplications of the MLL Gene in Acute Myeloid Leukemia: Prospective Analysis within the Multicenter Treatment Trial AML HD98-A
At the cytogenetic level clonal chromosome aberrations are identified in approximately 50% of all patients (pts) with de novo acute myeloid leukemia (AML). To identify subgroups of pts with differentExpand
Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm.
  • K. Döhner, K. Tobis, +4 authors H. Döhner
  • Medicine
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2002
TLDR
Within the subgroup of young adult AML patients with normal karyotype, MLL PTD is associated with short remission duration, and Multivariate analysis identified the MLLPTD status as the single prognostic factor for remission duration. Expand
Internal tandem duplications of the FLT3 and MLL genes are mainly observed in atypical cases of therapy-related acute myeloid leukemia with a normal karyotype and are unrelated to type of previous therapy
TLDR
FLT3/ITD and MLL/ITd are mainly observed in uncharacteristic cases of t-AML with a normal karyotype and unrelated to previous therapy for which reason they could represent sporadic cases of de novo AML. Expand
Acute myeloid leukemia with MLL rearrangements: clinicobiological features, prognostic impact and value of flow cytometry in the detection of residual leukemic cells
TLDR
In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene. Expand
Screening by fluorescence in situ hybridization for MLL status at diagnosis in 239 unselected patients with acute myeloblastic leukemia.
TLDR
All M2, M4, and M5 AML patients without known recurrent translocations should be investigated by FISH with an MLL probe because it allows the detection of MLL rearrangement that would go undetected by conventional cytogenetics and because it has the ability of detecting multiple copies of the MLL gene in, for example, marker chromosomes and double minutes. Expand
Analysis of FLT 3 length mutations in 1003 patients with acute myeloid leukemia : correlation to cytogenetics , FAB subtype , and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease
FLT3 length mutation (FLT3-LM) is a molecular marker potentially useful for the characterization of acute myeloid leukemia (AML). To evaluate the distribution of FLT3-LM within biologic subgroups, weExpand
Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease.
TLDR
Besides the importance of FLT3-LM for biologic and clinical characterization of AML, its value as a marker for disease monitoring based on 120 follow-up samples of 34 patients is shown. Expand
AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases.
TLDR
The category AML with 11q23/MLL abnormalities accounts for 2.8% of unselected AML, is closely associated with monocytic differentiation, and has a dismal prognosis. Expand
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References

SHOWING 1-10 OF 38 REFERENCES
Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics.
TLDR
The partial tandem duplication of ALL1 was responsible for ALL1 rearrangement in all such cases examined, making it a frequent molecular defect in adult AML patients with normal cytogenetics and thus require new therapeutic approaches. Expand
Partial duplication of the MLL gene in acute myelogenous leukemia without karyotypic aberration.
  • Y. Kwong
  • Biology, Medicine
  • Cancer genetics and cytogenetics
  • 1997
TLDR
This case of acute myelogenous leukemia (AML) M6 without karyotypic abnormality was found to have rearrangement of the MLL gene, the first reported case with an M6 phenotype, and highlights the importance of investigating for M LL gene mutations in all subtypes of AML, as they may carry prognostic significance. Expand
MLL tandem duplication and multiple splicing in adult acute myeloid leukemia with normal karyotype.
TLDR
It is found that seven of 34 patients diagnosed as having adult de novo, AML have a tandem partial duplication of exons 2 to 6 or 2 to 8 of the MLL gene, and these seven patients showed a median survival of 2.7 months, compared to a 6.8 months median survival for all other patients in the study. Expand
Tandem duplication of the MLL gene in myelodysplastic syndrome‐derived overt leukemia with trisomy 11
TLDR
Results indicated that a partial tandem duplication of exons 2‐8 of the MLL gene could be observed in MDS‐derived overt leukemia as well as de novo AML with trisomy 11. Expand
Partial tandem duplications of the MLL gene are detectable in peripheral blood and bone marrow of nearly all healthy donors.
TLDR
The data suggest that MLL duplications are not implicated in the malignant transformation in AML, or alternatively, that only a few cells will acquire additional oncogenic mutations necessary to establish themalignant phenotype of AML. Expand
The partial tandem duplication of ALL1 (MLL) is consistently generated by Alu-mediated homologous recombination in acute myeloid leukemia.
TLDR
Data support the hypothesis that a recombination event between homologous Alu sequences is responsible for the partial tandem duplication of ALL1 in the majority of AML cases with this genetic defect. Expand
ALL-1 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements.
TLDR
Sequence analysis of the genomic fusion region provides evidence for Alu-mediated homologous recombination as a mechanism for partial duplication of the ALL-1 gene. Expand
MLL self fusion mediated by Alu repeat homologous recombination and prognosis of AML-M4/M5 subtypes.
TLDR
Analysis of sequences at the duplication junction revealed that the points of MLL fusion within introns 6 and 1 both lie within Alu elements, which suggests the involvement of Alu repeat mediated homologous recombination in MLL self fusion. Expand
Partial duplication of HRX in acute leukemia with trisomy 11.
TLDR
The data indicated that HRX duplication is highly similar to the translocation affecting the HRX locus both in the restricted diversity of the fusion points and the involvement of Alu repeats within the breakpoint cluster region (exon 5 to 10). Expand
Molecular rearrangement of the ALL-1 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocations.
TLDR
It is concluded that molecular rearrangement of ALL-1 often can be detected in de novo AML, despite the absence of cytogenetic abnormalities involving 11q23. Expand
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