Biased Clonal Evolution in Acute Promyelocytic Leukemia through Imbalances Affecting the der(17) but Not the der(15) Chromosome: Report of Two Cases

Acute promyelocytic leukemia (APL) is characterized by the chromosomal translocation t(15;17)(q24;q21), raising two hybrid genes: PML::RARA and RARA::PML. There is a biased clonal evolution in APL since imbalances affecting the der(15) chromosome (the one that carries the transforming PML::RARA gene) have never been reported; instead, imbalances of the der(17), mainly in form of an ider(17)(q10), have been repeatedly documented. We here present two cases with APL who acquired an ider(17)(q10) as a secondary chromosomal change. The presence of the ider(17)(q10) implies several genomic consequences with potential to fuel tumor progression: (1) a duplication of the hybrid gene RARA::PML; (2) a cumulative haploinsufficiency for tumor suppressor genes located in the 17p arm; and (3) a cumulative triplosensitivity of genes located in 17q10→RARA::PML→15qter. Both our patients were treated following the PETHEMA LPA 2012 protocol with ATRA plus idarubicin and they have had a long event-free survival.

 

Comments：

Two cases of acute promyelocytic leukemia (APL) with the secondary chromosomal change of an ider(17)(q10) are presented, indicating potential genomic consequences, including gene duplication and sensitivity, that can fuel tumor progression and the patients were successfully treated with ATRA and idarubicin following the PETHEMA LPA 2012 protocol, resulting in a long event-free survival.

Related Products

Cat.No.	Product Name	Information
S1228	Idarubicin HCl	Idarubicin HCl (4-demethoxydaunorubicin (NSC256439, 4-DMDR) HCl) is a hydrochloride salt form of Idarubicin which is an anthracycline antibiotic and a DNA topoisomerase II (topo II) inhibitor for MCF-7 cells with IC50 of 3.3 ng/mL in a cell-free assay. Idarubicin induces mTOR-dependent cytotoxic autophagy.

Related Targets

Topoisomerase Antibiotics Autophagy