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Unbalanced translocation t(5;17) in an typical acute promyelocytic leukemia
V Brunel1, D Sainty, N Carbuccia
1Department of Biology, Institut Paoli-Calmettes, Marseille, France.
Abstract:
Acute promyelocytic leukemia (APL; M3 in the FAB classification) is specifically associated with the t(15;17)(q23;q12) and the consequent formation of a PML/RARA fusion gene. A few cases of APL with a t(11;17)(q23;q12) and a PLZF/RARA fusion gene have recently been reported. In addition, a new variant, t(5;17)(q32;q12), with a RARA rearrangement was described in a child with atypical APL. We report an unbalanced der(5)t(5;17) in an atypical APL case showing unusual dysgranulopoiesis and some M2 features. The breakpoints were difficult to localize precisely on chromosome 5, because the translocation may have occurred on a previous del(5q). The karyotype also showed del(8q) and multiple double-minutes (dmin). Molecular studies evidenced RARA rearrangement but showed neither PML rearrangement nor PML/RARA fusion. Fluorescence in situ hybridization revealed that the dmin were of chromosome 8 origin and that they accounted for the MYC amplification observed in Southern blots. The patient did very poorly despite chemotherapy and all-trans retinoic acid (ATRA) treatment. Thus, the t(5;17) could represent a second type of variant translocation in APL that, like the disease associated with t(11;17), does not seem to respond to ATRA therapy. Whereas RARA rearrangement appears sufficient for an APL-like phenotype, it seems that the presence of a classical PML/RARA is required for typical APL with response to ATRA.
Insights
A rare variant of acute promyelocytic leukemia (APL) involving a t(5;17) translocation and RARA rearrangement does not respond to standard ATRA therapy. This suggests RARA rearrangement alone can cause APL-like features, but PML/RARA fusion is needed for typical APL.
Area of Science:
- Hematology
- Cytogenetics
- Molecular Biology
Background:
- Acute promyelocytic leukemia (APL) is typically characterized by the t(15;17) translocation, forming the PML/RARA fusion gene.
- Variant translocations, such as t(11;17) with PLZF/RARA fusion, have been reported in APL.
- A t(5;17) translocation with RARA rearrangement has been described in atypical APL.
Observation:
- This study reports an unbalanced der(5)t(5;17) in an atypical APL case with unusual dysgranulopoiesis and M2 features.
- The karyotype also revealed del(8q) and multiple double-minutes (dmin), with fluorescence in situ hybridization confirming chromosome 8 origin of dmin and MYC amplification.
- Molecular studies confirmed RARA rearrangement but not PML rearrangement or PML/RARA fusion.
Findings:
- The t(5;17) translocation in this atypical APL case did not result in a PML/RARA fusion gene.
- The patient showed poor response to chemotherapy and all-trans retinoic acid (ATRA) treatment.
- RARA rearrangement alone may be sufficient for an APL-like phenotype.
Implications:
- The t(5;17) translocation represents a second type of variant translocation in APL that, similar to t(11;17), appears resistant to ATRA therapy.
- This finding suggests that the presence of the classical PML/RARA fusion gene is essential for typical APL and its response to ATRA.
- Further research into variant translocations in APL is crucial for understanding disease heterogeneity and developing targeted therapies.