3  Pathophysiology of APL

3.1 Variant RARA translocations and sensitivity to ATRA and ATO of the 12 fusion genes involving RARA

3.2 FLT3-ITD/TKD in APL

  • ~30-40% of APL
  • Leukocytosis, microgranular variant and involvement of the bcr3 breakpoint of PML
  • FLT3 ITD mutation is present in 25% of APL patients and is often associated with leukocytosis at presentation and M3v morphology.
  • However, unlike other AML sub-types, thepresence of the FLT3 ITD is not an independent predictor of increased risk of relapse in APL with current therapy.
  • However, the induction mortality may be higher in this subset given the association of FLT3 mutation with leukocytosis and risk of hemorrhagic death.
  • FLT3 inhibitors are not included in APL treatment.

3.3 Cryptic or masked t(15:17)

  • Cytogenetically cryptic
  • PML-RARA transcript detected molecularly (RT-PCR)

3.4 Secondary Cytogentic Abnormlaities

  • MSKCC data showing Epstein-Peterson et al. (2022)
  • Seen in ~40% of cases
  • Gain of chromosome 8 (most common; ~10-15% of cases)
  • Complex karyotype is associated with inferior event-free survival in patients who have APL treated with ATO.