AML gene expression profiling clusters

Introduction

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]:

More general terms

• acute myeloid leukemia (AML)