Acute promyelocytic leukemia (FAB type M3)

Only 1 case to date, a 59-years old male patient (Won et al., 2013).

The patient presented with anemia, thrombocytopenia, and high white blood cell count with 61% blasts and abnormal promyelocytes. BM aspirate revealed 69.2% microgranular abnormal promyelocytes. Immunophenotype analysis was positive for CD13, CD33, CD45, CD65, and MPO with negative CD34, HLA-DR, and B-cell and T-cell markers (data from Won et al., 2013).

Therapy with all-trans retinoic acid (ATRA) was initiated but it was discontinued after 2 days due to the negative PML/RARA molecular result. Induction therapy with idarubicin and cytarabine was started but ATRA was restarted 7 days later when RARA rearrangement was identified by fluorescence in situ hybridization (FISH). The patient achieved complete remission on day 28, and underwent allogenic stem-cell transplantation after 2 cycles of consolidation chemotherapy. He remains alive and in complete remission one year after transplantation.

The leukemic cells from the patient showed neutrophilic differentiation in the in vitro all-trans retinoic acid assay and the patient achieved complete remission with ATRA therapy, therefore NABP1/RARA fusion appear to be an ATRA-sensitive variant in APL.

Presented as der(2)t(2;17)(q32;q21).

RARA rearrangement by FISH.

t(11;19)(q13;p13.1) in a subclone.

5 NABP1 - 3 RARA

RARA portion of the transcript started in exon 3 and was fused in-frame to exon 5 of OBFC2A; breakpoint in RARA gene in the same breakpoint as in previously described fusions of RARA.

NABP1-RARA predicted to encode a 551-amino acid protein; NABP1 5-region encoding the DNA-binding domain (DBD) is fused to the 3-region of RARA including the DBD and ligand-binding domain (Figure 1. adopted from Won et al., 2013).

Patient with NABP1-RARA fusion shows a similar breakpoint within the RARA gene sharing a common portion as in other APL cases; therefore the chimeric protein is expected to behave as an altered retinoic acid receptor. The retention of the N-terminal oligonucleotide/oligosaccharide-binding fold in NABP1 protein that binds to single-stranded DNA substrate may provide the possibility of dimerization and produce oncogenic signaling leading to accumulation of undifferentiated promyelocytes.

NABP1/RARA