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AML gene expression profiling clusters

Gene expression profiling clusters [ref.1]: sixteen groups identified on basis of strong similarities - cluster 1: - some cases with 11q23 abnormalities - high levels of EVI1 expression - cluster 2: - >75% with normal karyotype - most with FLT3 internal tandem duplication which adversely affects outcome - cluster 4: - high frequencies of CEBPA mutations - upregulated T-cell genes CD7 and TCR delta - downregulated alpha1-catenin, tubulin beta 5, Nedd4 family interacting protein 1 - cluster 5: intermediate survival duration - FAB-M4 or FAB-M5 subtype - cluster 6: - >75% with normal karyotype - most with FLT3 internal tandem duplication which adversely affects outcome - cluster 8: - high frequency of monosomy 7 - cluster 9: favorable prognoss - includes AML with inv(16)(p13.1;q22.1);(CBF-beta/MYH11) - MYH11 most discrimitive gene - low level of CBF-beta - cluster 10: poor outcome - high levels of EVI1 expression - high frequency of monosomy 7, 5q loss, t(9;22) - cluster 11: - >75% with normal karyotype - cluster 12: favorable prognosis - cases of APL with t(15;17); PML-RAR alpha - genes for - hepatocyte growth factor (HGF) - macrophage stimulating 1 growth factor (MST1) - fibroblast growth factor 13 (FGF13) - two subgroups with high or low white count corresponding to presence of FLT3 internal tandem duplication which adversely affected outcome - cluster 13: favorable prognosis - includes AML with t(8;21)(q22;q22); AML1/ETO - ETO most discriminate gene - interleukin 5 receptor alpha - cluster 15: - high frequencies of CEBPA mutations - downregulated alpha1-catenin, tubulin beta 5, Nedd4 family interacting protein 1 - cluster 16: - some cases with 11q23 abnormalities - high levels of EVI1 expression not apparent Gene expression profiling clusters [ref.2]:

General

acute myeloid leukemia (AML)

References

  1. Valk et al. NEJM 360:1617-1628, 2004 http://content.nejm.org/cgi/content/short/350/16/1617 supplementary http://content.nejm.org/cgi/content/full/350/16/1617/DC1
  2. Bullinger et al. NEJM 360:1605-1616, 2004 http://content.nejm.org/cgi/content/short/350/16/1605