Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: a concise review

  title={Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: a concise review},
  author={Claudia Dorothea Baldus and Krzysztof Mr{\'o}zek and Guido Marcucci and Clara Derber Bloomfield},
  journal={British Journal of Haematology},
Normal cytogenetics are detected pretreatment in approximately 45% of patients with de novo acute myeloid leukaemia (AML); thus this constitutes the single largest cytogenetic group of AML. Recently, molecular genetic alterations with prognostic significance have been reported in these patients. They include internal tandem duplication of the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA and NPM1 genes and aberrant expression of the BAALC, ERG and MN1 genes… 

Array-based cytogenetic approaches in acute myeloid leukemia: clinical impact and biological insights.

Investigations have revealed that AML genomes commonly harbor acquired submicroscopic copy number alterations, even though the prevalence of most of these cryptic lesions appears to be low, as well as regions of uniparental disomy that are often associated with homozygosity of functionally relevant gene mutations.

Mutation of FLT3 gene in acute myeloid leukemia with normal cytogenetics and its association with clinical and immunophenotypic features

FLT3/ITD mutation was found to be associated with the age, leukocytosis and aberrant expression of CD7, although no influence of FLT3/(ITD) mutation was seen on the clinical outcome of AML patients with normal cytogenetics.

FLT3 mutations have no prognostic impact in elderly patients with acute myeloid leukemia and normal karyotype

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Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype

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The results demonstrate that molecular biology and FISH studies provide relevant information in AML and should be routinely performed.

Cytogenetic Profile of de novo Acute Myeloid Leukemia Patients in Malaysia

The karyotypic patterns of 480 patients with de novo AML seen at government hospitals throughout the country were examined and the association of chromosome aberrations with the age of patient was evaluated to show different cytogenetic abnormalities in AML show different frequencies with increasing age.

Cytogenetic abnormalities in adult non-promyelocytic acute myeloid leukemia: a concise review.

Aberrant expression of CD7 in myeloblasts is highly associated with de novo acute myeloid leukemias with FLT3/ITD mutation.

Clinical and pathologic features of 15 cases of de novo AML with normal cytogenetics and with the FLT3/ITD mutation suggest that FLT 3/ ITD- mediated leukemic transformation occurs in the more early stage of myeloid progenitor cells.

Acute myeloid leukemia with DNMT3A mutations

Data suggest that mutations in the DNMT3A gene represent a novel class of mutations in AML with distinct biological and clinical features, which are found to be associated with cytogenetics, age, white blood cell count, prognosis and response of patients to chemotherapy.



Clinical importance of cytogenetics in acute myeloid leukaemia.

Current information on chromosome abnormalities in AML, and on associations between karyotype and clinical characteristics and outcome of AML patients are presented.

Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?

Proper prognostic genetic findings in karyotypically normal AML are reviewed and clinical implications are discussed, since many of the identified genetic alterations already constitute or will potentially become targets for specific therapeutic intervention.

BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: a Cancer and Leukemia Group B Study.

It is concluded that high BAALC expression predicts an adverse prognosis and may define an important risk factor in AML with normal cytogenetics.

BAALC expression and FLT3 internal tandem duplication mutations in acute myeloid leukemia patients with normal cytogenetics: prognostic implications.

This study strengthens BAALC expression as one of the most important prognostic factors in AML patients with normal cytogenetics and FLT3 mutation status should assist in tailoring induction and postremission therapies.

The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties.

Subgroup analysis demonstrated that the three cytogenetically defined prognostic groups retained their predictive value in the context of secondary as well as de novo AML, within the pediatric age group and furthermore were found to be a key determinant of outcome from autologous or allogeneic bone marrow transplantation (BMT) in first CR.

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In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene.

Risk Assessment in Patients with Acute Myeloid Leukemia and a Normal Karyotype

It is found that high BAALC expression in normal-karyotype AML with neither FLT3-ITD nor CEBPA mutations indicates adverse prognosis for both DFS and OS, and represents a novel prognostic marker.

Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics.

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.

Cytogenetics in acute leukemia.

Current views on clinical relevance of major cytogenetic findings in adult AML and ALL are summarized.

Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm.

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