Childhood Acute Myeloid Leukaemia (childhood + acute_myeloid_leukaemia)

Distribution by Scientific Domains


Selected Abstracts


The prognostic significance of cytogenetic aberrations in childhood acute myeloid leukaemia.

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2007
A study of the Swiss Paediatric Oncology Group (SPOG)
Abstract In childhood-onset acute myeloid leukaemia (AML) the clinical value of karyotypic aberrations is now acknowledged, although there is still debate concerning the prognostic significance of some events. To add to this knowledge, cytogenetic analysis was performed on a consecutive series of 84 childhood AML patients diagnosed in Switzerland. A result was obtained for all patients, with 69 (82%) showing a clonal karyotypic aberration. In the remaining 15 (18%), no karyotypic aberration was seen by either conventional or fluorescence in situ hybridisation analyses. The most frequent aberrations observed were t(11q23) (19% of all patients), t(8;21) (12%) and +8 (11%). Except for cytogenetics, no clinical parameter was shown to be significantly associated with outcome. The analysis of individual cytogenetic subgroups demonstrated that aberrations involving chromosome 16q were the strongest predictor of a good prognosis, while +8 and complex karyotypes represented the strongest predictors of a poor prognosis. It was also noteworthy that patients with the rare aberrations of del(11q) (n = 4) and t(16;21)(p11;q22) (n = 3) had a poor outcome. The results support the importance of cytogenetic analysis in childhood AML, but show that further work is required in the classification of the poor prognosis aberrations. [source]


Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukaemia: towards definition of a new leukaemia entity,

HEMATOLOGICAL ONCOLOGY, Issue 4 2009
Rachel Rau
Abstract Nucleophosmin (NPM) is a ubiquitously expressed chaperone protein that shuttles rapidly between the nucleus and cytoplasm, but predominantly resides in the nucleolus. It plays key roles in ribosome biogenesis, centrosome duplication, genomic stability, cell cycle progression and apoptosis. Somatic mutations in exon 12 of the NPM gene (NPM1) are the most frequent genetic abnormality in adult acute myeloid leukaemia (AML), found in approximately 35% of all cases and up to 60% of patients with normal karyotype (NK) AML. In children, NPM1 mutations are far less frequent, occurring in 8,10% of all AML cases, and in approximately 25% of those with a NK. NPM1 mutations lead to aberrant localization of the NPM protein into the cytoplasm, thus the designation, NPMc+ AML. NPMc+ AML is seen predominantly in patients with a NK and is essentially mutually exclusive of recurrent chromosomal translocations. Patients with NPM1 mutations are twice as likely as those who lack an NPM1 mutation to also have a FMS-like tyrosine kinase (FLT3) internal tandem duplication (ITD) mutation. NPMc+ AML is also characterized by a unique gene expression signature and microRNA signature. NPMc+ AML has important prognostic significance, as NPMc+ AML, in the absence of a coexisting FLT3-ITD mutation, is associated with a favourable outcome. NPM1 mutations have also shown great stability during disease evolution, and therefore represent a possible marker for minimal residual disease detection. Given its distinctive biologic and clinical features and its clear clinical relevance, NPMc+ AML is included as a provisional entity in the 2008 WHO classifications. There is still much to be learned about this genetic alteration, including its exact role in leukaemogenesis, how it interacts with other mutations and why it confers a more favourable prognosis. Further, it represents a potential therapeutic target warranting research aimed at identifying novel small molecules with activity in NPMc+ AML. Copyright © 2009 John Wiley & Sons, Ltd. [source]


In vitro efficacy of l -asparaginase in childhood acute myeloid leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2003
Shuichi Okada
Summary., To explore the potential efficacy of l -asparaginase treatment in acute myeloid leukaemia (AML) patients, we studied the in vitro resistance of French,American,British (FAB) subtypes of childhood AML to l -asparaginase using a methyl,thiazol,tetrazolium assay. We tested leukaemic cells obtained from 177 common acute lymphoblastic leukaemia (cALL) and 228 AML children at diagnosis. The median 70% lethal dose of l -asparaginase (LD70asp) (U/ml) was 0·46 in the cALL and 6·70 in the AML samples. The median LD70asp among each FAB subtype of AML was 0·76 (M0), 0·46 (M1), 10·00 (M2), 10·00 (M3), 1·18 (M4), 1·35 (M5) and 10·00 (M7). Type M3 samples had the highest LD70asp. The LD70asp of the M2 samples was significantly higher than that of the M1, M4 and M5 samples. When the LD70asp values were classified as low (0·016,0·159), intermediate (0·16,1·59) or high (1·6,10·00), the frequency of low, intermediate or high LD70asp among the M1 samples were similar to those among the cALL samples. In conclusion, cells from AML types M1, M4 and M5 were relatively sensitive to l -asparaginase, and M1 cells were as sensitive as those of cALL, suggesting that l -asparaginase treatment may be effective for these subtypes of AML. [source]


Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia

BRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2003
Elaine Coustan-Smith
Summary. In children with acute myeloid leukaemia (AML), morphological and karyotypic studies cannot precisely assess response to treatment, and less than one-third of patients have genetic markers for molecular studies of residual disease. We determined the usefulness of a four-colour flow cytometric strategy developed in our laboratory to study residual disease. We first compared the immunophenotypes of AML cells obtained from 54 children at diagnosis with those of cells from 59 normal or regenerating bone marrow samples. Forty-six of the 54 AML cases (85·2%) had immunophenotypes that allowed detection of 0·1,0·01% residual leukaemic cells. Of 230 bone marrow samples obtained from those 46 patients during and off treatment, 61 (26·5%) had ,,0·1% AML cells by flow cytometry. We found that core binding factor-associated AML had a significantly better early treatment response. Mean (± standard error) 2-year survival estimate was 33·1 ± 19·1% for patients with ,,0·1% AML cells by flow cytometry after induction therapy, but 72·1 ± 11·5% for those with <,0·1% AML cells (P = 0·022); overt recurrence of AML within the subsequent 6 months was significantly more likely in the former group. The assay described here holds promise for guiding the choice of post-remission treatment options in children with AML. [source]