Genetic alterations in childhood ALL (2015)

My notes on the following paper. -Patty Feist

A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia (ALL). Moorman AV et al., Blood, epub 2014 Jun 23. Abstract.

This paper refines risk by how the poor-risk secondary abnormalities coexist with each other and with other high risk genetic subtypes. The goal is to determine a sub-set of childhood ALL that can have a less intensive treatment, so they can then focus on future treatment strategies for these patients, strategies that can focus on deintensification, compliance, and targeted therapies.

Good risk genetic features included ETV6-RUNX1, high hyperdiploidy, normal copy number status for the eight most commonly deleted genes, isolated deletions affecting ETV6/PAX5/BTG1, and ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/B. All other genetic features were classified as poor risk.

What I find useful is the following definitions of "good" and "poor" risk genetic abnormalities.

Good risk genetic abnormalities

good risk cytogenetic abnormalities

  • ETV6-RUNX1/t(12;21)(p13;q22)
  • high hyperdiploidy (51-64 chromosomes)

good risk copy number alteration profiles

  • no deletion of IKZF1, CDKN2A/B, PAR1, BTG1, EBFI, PAX5, ETV6, RB1
  • isolated deletions of ETV6, PAX5, OR BTG1
  • ETV6 deletions with a single adtiional deletion of BTG1, PAX5, or CDKN2A/B

Poor risk genetic abnormalities

high risk cytogenetic subgroups

  • t(9;22)(q34;q11)/BCR-ABL1
  • MLL/11q23 translocation
  • near haploidy (<30 chromosomes)
  • low hypodiploidy/near triploidy (30-39/60-78 chromosomes)
  • intrachromosomal amplification of chromosome 21 (iAMP21)
  • t(17;19)/q23;p13)/TCF3-HLF

intermediate and poor risk copy number alteration profiles

  • any deletion of IKZF1, PAR1, EBF1 or RB1
  • all other copy number alteration profiles not mentioned above